- "I've always been fighting my destiny, trying to avoid becoming my father. But we all have certain genes that, no matter how much we want to change, dominate us." - Lex Luthor, Exodus
In the wake of the tornado, Lex got his father to the hospital and approved a surgery which failed to save Lionel's eyesight. He helped Clark find Jonathan, and later saved Jonathan from being killed by Nixon by shooting the reporter with a handgun. Jonathan finally gave up his mistrust of Lex, and the two attempted to forge a positive relationship. During the summer, Lex helped Chloe Sullivan out on a story at the Daily Planet, as well as provided a means of escape when she and Pete Ross were on the run.
Lex was briefly married to Desiree Atkins while under the influence of her super pheromones. She would use his influence to turn him against Clark and close down the Talon. Lex would soon after include a policy to give Lana more authority over the Talon. During his stay at the mansion, Lionel had been insisting and approving for accommodations to compensate for his blindness to Lex's dismay. Meanwhile, he helped Jonathan find Clark when he ran away from home. Later, Lex told Lionel that he refused to give him self-pity and removed his changes to the office.
When Rachel Dunleavy (Lucas' mother) arrived in town claiming to be Clark's biological mother, Lex thought that Clark was his brother, but it turned out to be false. Lex and Lionel also fought over control of the Kawatche Caves. When Lex met Mayor William Tate, discovered him to be corrupt, and supported his opponent in the next election. He also ensured that the Kents would have custody over Ryan when it was discovered that he was being held under observation at Summerholt.
Lex and Helen Bryce met at the hospital after Jonathan broke his leg. Though she is hesitant to enter a relationship as she remembered a previous encounter at Metropolis ER. They broke up when Lex suspected Helen of spying on him, but they worked it out and got back together. Lex spent a good deal of the year trying to protect LexCorp from his father's attempts to acquire it. He later discovered that Lionel bugged the mansion, and attempted to bug LuthorCorp.
Lionel was later shot after his takeover of LexCorp with Lex being one of the suspects. Afterward, Lex left Metropolis to meet Malcolm Barnes (a friend from prep school), as he claimed to have made a breakthrough on the cave's hieroglyphics. When he arrived, Malcolm was discovered to be dead, with notes that claimed Lex to be the killer. He was eventually apprehended by the FBI and informed that his Swiss bank account is emptied. With Clark's help, he managed to retreat and decided to visit Lionel with the intent to shoot him.
Lionel was accused of his account being stolen, only to discover that the money was still there until a recent withdrawal was made. Lex was then escorted out by security, only to discover that the guards were FBI Agents, prompting him to escape. He get a Taxi ride only to discover that the driver was the cop who discovered Malcolm's death. After evading a gunfire, Lex discovered that the FBI Agents were all hired actors, with Malcolm behind the charade.
The intent was for Lex to be arrested for killing Lionel, so that his employer would get control of LuthorCorp while he would get the contents of Lex's bank account. The employer was revealed to be Dominic Sanatori, whom Lex met up with in his limo. Lex declared war on Dominic, and then pushed him out of the limo (which was traveling at 40 miles per hour). When his long-lost half-brother Lucas Luthor and Lionel kicked Lex out of the mansion, Lex stayed with the Kents and did chores around the farm. Afterwards, Lex finally secured his company again with the help of Lucas.
Helen gave up a fellowship and moved into the mansion with Lex. He made a great leap forward and showed real trust when he shared with Helen his room of obsessions. When an ex-boyfriend showed up in Smallville and beat her within an inch of her life, he very nearly killed him, but it was his love for her that pulled him back from the edge. That's when he decided to propose to her. During this time, he helped Lana to learn how to fight after she was attacked at the Talon.
Lex invited Jonathan and Martha Kent to the wedding rehearsal dinner for Lex and Helen, with Jonathan standing in for Lionel. They broke up again, when she learned that he stole something from her office, but Lex managed to dig deep and beg forgiveness. They were finally married, but while flying to their honeymoon, something went terribly wrong. Lex woke up to find the plane empty and crashing.