Helen first met Lex many years ago when he visited the emergency room in Metropolis. She was the intern assigned to sober him up. Experiences like that helped her decide to leave Metropolis and her father's offer to join his practice and move to Smallville.
- "I can't even begin to fathom the depths of the Luthor family pathology… I'm glad that this happened. It showed me who I was really dealing with. You know, I've done some pretty stupid things in my life, but this could possibly win the Nobel Prize for stupidity. I fell for someone who never really existed." -Helen Bryce, Visage
Lex did not recall this encounter the next time he met Helen while visiting Jonathan Kent in the hospital. Lex offered to have a specialist flown in from Metropolis to mend Jonathan's broken leg. Helen was a bit offended that he didn't think her capable of the task.
They ran into each other again in an anger management class. She was ordered to attend after "drop-kicking" an orderly. Helen turned down Lex's first invitation to go out together saying that she had met him before. Later, Lex sought her out at the hospital; apparently he did some research to jog his memory. He apologized for his previous behavior in Metropolis explaining that she met him during his self-destructive phase, and she agreed to go out with him and they began dating.
However, their relationship was further complicated by Lex's scheming father Lionel. Lex received photographs of Helen with Lionel Luthor as part of his surveillance of Lionel. He ordered a complete background check on Helen and discovered that she received $100,000. He accused her of spying on him. She was so angry that he had her investigated that she broke up with him on the spot. Later, Lex found her at the Talon and asked for an explanation. She told him that Lionel offered her money to stop seeing Lex, she refused, but Lionel wired the money anyway.
Lex apologized, but Helen didn't want to be a pawn in Lionel's game with Lex. Lex approached her again at the hospital and begged her to take him back. He said that he needed her to help him resist becoming his father, and they reconciled.
Helen considered accepting a research grant at Johns Hopkins but Lex asked her to move in with him. She had reservations, and postponed a decision, but after she moved in, she found a locked room. She asked Lex about it. He didn't want to show it to her, and she thought she could be okay with that, but she finally decided that if they were going to be more than roommates, he had to show it to her. It was filled with Lex's evidence of his suspicions about Clark and his family.
When Clark's blood sample was stolen from Helen's office, Lex denied knowing anything about it, but finally revealed that he was the one who broke into her office and stole the blood sample. She called off the wedding and left Smallville, but ultimately decided that she loved Lex and forgave him just hours before the wedding.
Lex and Helen's plane crashed in the Caribbean leaving Lex stranded while Helen returned to Smallville to tell Lionel that she and Lex woke up to find the pilot missing and there was only one parachute. She said that Lex insisted that she use it and Lex went down with the plane. Helen spoke at Lex's funeral, but Lionel was convinced that her story was a lie, and she that murdered Lex, so he refused to stay and hear her words. Lex, while on the island, was doing everything he could to get back to Helen despite suggestions from his "imaginary friend" that she had betrayed him.
Lex later escaped the island and demanded Lionel to know where Helen was and was surprised to find out that she was alive and well in his mansion. Lionel told Lex Helen's version of their plane crash that the pilot bailed and left them with only one parachute. Lex sacrificed himself by giving it to Helen but Lionel said he didn't believe her. Lex refused to believe that Helen was responsible and Lionel pointed out that he had nothing to gain, but Helen was now one of the richest women in the world. He said to Lex to ask her about the vial of blood that he returned to her. Later, Lex approached Helen in the Luthor Mansion and she told him another version of the story that they had been drugged by the pilot and she couldn't wake Lex. She took the only parachute and left him. He asked her about the vial, and she explained Lionel promised if she gave it to him he'd leave them alone. She told Lex that she will comply if he wanted to get the marriage annulled but that she does love him. Helen later told Lex that she was leaving for a while to give him space. Lex surprised her by asking if they could give their honeymoon a second try. On board their private jet, Lex revealed that he still thought Helen tried to kill him. He had done some research and discovered that the area where he was found was unreachable with the amount of fuel they took off with, so he investigated every island in the area and discovered that Helen landed in St. Croix at 7:59 PM. He guessed that Helen drugged him and paid the pilot to drop her off and crash the plane with Lex inside. Helen pulled out a gun and Lex tried to take it from her; in the struggle, they shot the pilot. The plane started to go down and Lex rushed into the cockpit to take over the controls, while Helen parachuted away. Lex later had search parties try and find but came to the conclusion that she wouldn't be found until she wanted to be.