Main villains of the Smallville universe.
- Main Antagonist: Roger Nixon
- Supporting Antagonists: Freak of the week and Lionel Luthor
- Other Notable Antagonists: Sam Phelan
This season originally started with the freaks of the week as the main antagonists. However, the show introduced Roger Nixon. He became a recurring character who was a reporter that was hired by Lex to investigate the strange circumstances that surrounded his accident on the bridge. As he came closer to discovering Clark's secret, by the end of the season, he turned into a villain, as he almost killed Jonathan Kent during the tornado.
- Main Antagonists: Lionel Luthor
- Supporting Antagonists: Kal and Frederick Walden
- Other Notable Antagonists: Freak of the week, Ethan Miller, and Jor-El
Freaks of the week continued to provide a regular threat for Clark to overcome, although this season also introduced more ongoing threats, including Clark himself. Lionel became a more important character, as he began to interfere with Lex's day-to-day life. He upset numerous people in Smallville and was eventually shot by long-time friend of the Kents and Sheriff of Smallville, Ethan Miller. Lionel recovered, but Ethan was arrested.
Red kryptonite showed that there was a villainous side to anyone, as Clark was infected and went on a rampage. Frederick Walden was hired by Lex to investigate the Kawatche Caves, which led to him discovering Clark's secret. His time in the caves resulted in him absorbing Kryptonian knowledge, which sent him into a coma. He awoke with the ability to emit energy. During a fight with Clark, Dr. Walden was killed, but an imprint of the Kryptonian Key was left on his hand, which Lionel used to make a duplicate key out of Kryptonite, in an attempt to discover Clark's secret.
The end of the season introduced Jor-El, who seemed to be a big threat to Clark's human life, which he continued to be in Season Three.
- Main Antagonist: Lionel Luthor
- Supporting Antagonists: Morgan Edge and Adam Knight
- Other Notable Antagonists: Jor-El, Frank Loder, Helen Bryce and Kal
Helen Bryce and Kal started off the season as small threats, although both were overcome within 2 episodes, whereas Morgan Edge, who was also introduced in the season premiere, became a recurring villain. Although Edge originally met Kal, he quickly discovered his alter ego and almost revealed it to Lionel, who was looking for the source of a vial of special blood that was stolen from Helen Bryce. Despite assuming that Edge died in an explosion, he reappeared later with the dangerous knowledge of Clark's weakness to Kryptonite. Edge conspired with Lionel to break Lex's fragile psyche, but Clark stopped him.
Lionel Luthor became more villainous this season, sending Lex to a mental asylum and even erased his memories. He was eventually incarcerated for the murder of his parents. Jor-El also became more of a threat. Despite originally coming to an agreement with Jonathan Kent to help bring Clark back from his red kryptonite-induced exile, Jor-El still wanted Clark to give up his human life and accept his Kryptonian heritage. He began sending messages to Jonathan, which put a strain on the family and eventually he sent a reprogrammed girl, who had been made to believe that she was Kara from Krypton, to convince Clark to submit himself to Kryptonian training. When Jonathan tried to prevent this, Jor-El put him in a coma.Adam Knight and Frank Loder, both working with the Luthors, are recurring villains who looked into Clark's secret. Just as Frank discovered the truth, Kara killed him. Adam acted as Lana's friend to try to uncover the truth through her in exchange for Lionel's help to get a serum that was helping to keep him alive. Once he alienated Lana, Lionel stopped his access to the serum, which sent Adam on a desperate rampage that almost killed Lana.
- Main Antagonists: Genevieve and Jason Teague
- Supporting Antagonists: Margaret Isobel Thoreaux
- Other Notable Antagonists: Lionel and Lex Luthor
This season introduces the first Big Bad to never meet Clark Kent personally, Genevieve Teague, a character that was introduced halfway through the season. All of the primary villains of this season came about, as a result of the Stones of Power. The Teagues were searching for the stones and would go to any great lengths to get them, including killing Bridgette Crosby. The Teagues were linked to Margaret Isobel Thoreaux, an evil witch and Lana's ancestor. Thoreaux wanted to kill the Teagues, as their ancestors had been responsible for burning her at the stake. She was able to exact her revenge through the stones, which enabled her to take over Lana's body.
Lionel started the season in prison for murdering his parents. He continued his villainous ways by employing an assassin to kill Chloe Sullivan and using one of the stones to transfer bodies with Clark. This was a key moment in Lionel's life, as it cured him of a fatal liver disease. After this, his motives became more righteous, such as trying to get ahold of the stones on Lana's behalf, rather than his usual selfish reasons. However, he still sometimes went about things in the wrong way, as he resorted to poisoning Genevieve to get the stone and even shot Jason to stop him from revealing Clark's secret to Lex.
Lex Luthor became more villainous here than in the previous seasons, doing what he had to get the stones and even becoming the Lex we know and love from the comics in one episode. He also took advantage of Clark's amnesia as another attempt to discover his secret.
- Main Antagonist: Brainiac
- Supporting Antgonists: Lex Luthor and Zod
- Other Notable Antagonists: Disciples of Zod
In another meteor shower, the Disciples of Zod arrived on Earth. They terrorized Smallville in their search for Kal-El, in hopes that he would join them. When Clark refused, they tried to send him to the Phantom Zone. However, Clark managed to send them there instead. It soon became clear that they did not arrive alone, as Brainiac came out of their ship. He quickly disguised himself as Clark's college tutor, Milton Fine, until he saved Clark from silver kryptonite. It was revealed that this was part of Brainiac's manipulation, as he had caused the silver kryptonite infection. When Martha became sick, Brainiac blamed Jor-El, in an attempt to turn Clark on his father, explaining that he had been a violent dictator who fought against "the voice of the people," Zod.
Brainiac convinced Clark to destroy the Fortress, but in doing so, he almost released Zod from the Phantom Zone. Zod was eventually released during the events of Dark Thursday, after Brainiac had prepared Lex to be the vessel.
Lex became more villainous throughout the season. With his friendship with Clark effectively ruined, he went to desperate measures to discover his secret by sending three escaped criminals to hold Lana and the Kents hostage. However, during that time, Clark had been made mortal by Jor-El, as a punishment for not completing his training. Lex also stole Lana away from Clark by employing Simone Charcot to seduce Clark into revealing his secret and splitting up Lana and Clark. Lex then began to work with Brainiac, which led to him becoming the vessel for Zod.
- Main Antagonist: Lex Luthor
- Supporting Antagonists: The Phantom Zone Criminals and Bizarro
- Other Notable Antagonists: Zod and Disciples of Zod
Zod sent Clark to the Phantom Zone in the season finale and, during Clark's absence, Zod puts his plan into motion to transform Earth into New Krypton. This involved stealing technology from the Pentagon to cause a major earthquake across Metropolis. He also kept Lana hostage, in an attempt to use her to get himself an heir.
While Clark was in the Phantom Zone, he encountered the Disciples of Zod, who attempted to get their revenge by trying to kill Clark. Thanks to Raya's help, Clark escaped from the Phantom Zone and quickly defeated Zod, although he caused several other extra terrestrial criminals to escape, including Bizarro. Clark tracked down these villains one by one, although it took all season to find Bizarro, who eventually cloned himself from Clark's DNA.
Lex continued his descent into evil, due to his desperation to keep Lana for himself. He faked Lana's pregnancy to make her agree to marriage. When this secret was almost exposed, he killed their doctor. This eventually led to Lana leaving him and faking her own death to set up Lex for murder. He also continued to experiment on meteor freaks and the Phantom Zone criminals, in order to make an army of super freaks.
- Main Antagonist: Lex Luthor
- Supporting Antagonists: Brainiac and Bizarro
- Other Notable Antagonists: Zor-El and Edward Teague
Once he cloned himself from Clark's DNA, Bizarro became more powerful, causing Reeves Dam to burst. He killed anyone that got in his path, but Clark realized that he was weakened by sunlight. With Martian Manhunter's help, Clark defeated Bizarro.
Clark encountered a replicant of his Kryptonian uncle, Zor-El, who caused a solar eclipse to turn Earth into New Krypton. Clark managed to stop Zor-El once he destroyed the blue crystal that Zor-El and Lara-El emerged from. However, during the eclipse, Bizarro escaped and returned to Earth. Jor-El punished Clark for releasing Zor-El by encasing him in ice. During this time, Bizarro began living Clark's life with Lana. To avoid his secret being discovered, he teamed up with Brainiac, who was gradually repairing himself. Brainiac double crossed Bizarro and led Clark to discover that blue kryptonite would destroy Bizarro. However, Brainiac did this for selfish reasons, merely to track down Dax-Ur, his creator.
Once Brainiac was repaired, he attacked Lana, kidnapped Kara and tried to kill baby Kal-El back on Krypton. Clark time-traveled back to the day of Krypton's destruction to stop him. However, Brainiac disguised himself as Kara and came back with Clark to reveal the truth to Lex.
Lex had gradually been getting closer to Clark's secret throughout the season by manipulating Kara, during her amnesia, and investigating Lionel's past connections with a secret society named Veritas. Lex eventually resorted to murdering his father to get to the truth, as he discovered that Veritas intended to control the Traveler. This led him to Edward Teague, who turned on Clark for the sake of the world, as without the Traveler, Lex would not be able to control him.
Lex eventually confronted Clark at the Fortress and inserted the alien orb, which caused the Fortress to collapse and remove Clark's powers.
- Main Antagonist: Davis Bloome
- Supporting Antagonists: Brainiac and Lex Luthor
- Other Notable Antagonists: Tess Mercer and Winslow Schott
During the course of this season, Davis Bloome, the human disguise for Doomsday, came into Clark's life and quickly became a love interest for Chloe, who was under the influence of Brainiac. Brainiac was initially interested in self-preservation, after he was weakened by Chloe's meteor power. As he gradually built his strength by removing Chloe's memories, he made a connection with Doomsday to destroy Earth once he has absorbed all the knowledge of the planet. However, Brainiac was removed from Chloe by the Legion of Super-Heroes.
Once Davis had become aware of his past, it became harder for him to control the beast inside. Chloe tried to help for Clark's benefit, as she knew Doomsday would kill Clark. Black Kryptonite eventually split Davis from Doomsday and Clark buried Doomsday alive. Davis, meanwhile, proved to be just as evil as his Kryptonian counterpart, as he killed Jimmy in a jealous rage.
With Lex's apparent demise in the Arctic, Tess Mercer took over LuthorCorp and seemed to go to any lengths to discover what happened to Lex. She was very manipulative, even resorting to blowing up the plane that she and Clark were on to expose his secret. Tess turned on Lex, however, when she discovered (through Lana) that he had inserted microchips in her. This resulted in Lex re-emerging, despite being in a weakened state. He employed Winslow Schott to exact his revenge on Clark and Lana by making Lana absorb Kryptonite, thus preventing them from being a couple. After this, Lex was killed in an explosion by Oliver.
- Main Antagonist: Major Zod
- Supporting Antagonsists: Tess Mercer and Amanda Waller
- Other Notable Antagonists: John Corben, Icicle and Ray Sacks
Major Zod and his Kryptonian Army were released from the orb after Doomsday's defeat. They quickly teamed up with Tess to give them their powers. They began experimenting on humans, including John Corben, to try different ways to get powers. By doing this, they turned Corben into a villain, who went after the Blur for revenge for allowing his sister to die.
Ray Sacks, Metropolis DA, also resented the Blur for being a vigilante. He desperately tried to discover his identity without caring who got hurt. He even attempted to kill Lois.
It became clear the Tess was a double agent, as she was also affiliated with Checkmate, who were trying to defeat the Kandorians. They even resorted to sending Icicle on a killing spree to reunite the Justice Society to help with their fight against the Kandorians.
Once they got their powers from Clark's blood, the Kandorians got the upper-hand on Checkmate and Zod destroyed their facility, killing many of their operatives. Zod and the Kandorians realized that they couldn't fit in on Earth and started to attack Earth. However, Clark defeated them by using the Book of Rao to send them to another plane of existence.
- Main Antagonist: Darkseid
- Supporting Antagontists: Lionel Luthor (Earth-2) and Darkseid's prophets (Granny Goodness, Desaad, and Gordon Godfrey)
- Other Notable Antgonists: Slade Wilson, Zod, Clark Luthor, Lex Luthor, Marionette Ventures, Suicide Squad, and Winslow Schott
The season started with a clone of Lex Luthor that began to terrorize Clark and killed every single Lex clone except for Alexander. The episode also brought the possibility of the Suicide Squad appearing as villains, and ended up with an appearance of Darkseid, who would return later in the body of a man, trying to convince people that the superheroes are a menace. Slade Wilson, a villain from the comics, appears in two episodes. Lionel Luthor also returned in the form of an alternate universe version of himself. Lionel and Slade are a part of Darkseid's plan. General Zod also returned, merging with his younger clone's body and took over the Phantom Zone, and was also revealed to be an ally of Darkseid. In the series finale, Lex Luthor also returned, thanks to Darkseid's help. Clark's Earth-2 counterpart, Clark Luthor, was also an antagonist for two episodes.
- Main Antagonist: Monitors and Lex Luthor
- Supporting Antagontists: Hank Henshaw, The Prankster, Mr. Freeze, White Martian, Black Flash, Metallo, Kirt Niedrigh, Hades, Rose Wilson, Brother Blood, Parallax
- Other Notable Antagonists: Doomsday, Felix Faust, Bones, Bruce Wayne (parallel Earth), Manhunters, Prometheus, Yellow Lantern Corps
- While freaks of the week only served in the beginning to further Clark and Lex's relationship with time that idea was dropped and the show tried to build a completely different mythology from the one in the comics.