Karen makes her debut in Daredevil #1. Foggy Nelson hires her to be the secretary for his and Matt Murdock’s new law firm, Nelson and Murdock. Karen is beautiful, young, innocent, and naïve. She is infatuated with Matt from the moment they meet, but she also soon becomes mesmerized by the Daredevil, Matt’s crime fighting alter ego.
Karen's father, Doctor Paxton Page, fakes his own kidnapping and death so that he can assume the guise of the villain "Death's-Head." Karen returns to her parents' home to investigate her father’s disappearance. Daredevil follows her. In the ensuing battle between Daredevil and Death’s Head, Death’s Head spills a vat of molten cobalt over Daredevil, but realizes that Karen is endangered. This brings him back to his senses, and he pushes Daredevil and Karen to safety. He appears to die in this act of self-sacrifice, when he is coated in the molten cobalt.
After the battle with Death’s Head, Daredevil reveals his true identity to Karen. She is conflicted, as she is in love with both Matt the man and Daredevil the hero. She constantly fears for Matt’s safety, but he can not give up fighting crime. Karen eventually leaves him and moves to California to pursue an acting career. She finds work as an actress in a daytime soap opera.
Karen then becomes addicted to heroin and starts making pornographic movies. In the "Born Again" story arc, Karen, in need of a fix, sells Daredevil's secret identity to a drug dealer, who in turn sells it to the Kingpin. Karen is forced to return to New York, where she meets up again with Matt. He helps Karen beat her addictions and straighten up her life. Karen eventually resumes her relationship with Matt.
During the Typhoid Mary storyline, Karen discovers that Matt has a romantic history with Mary, and she and Matt break up again. They eventually reunite, however. She becomes an anti-pornography activist and even assists Daredevil and the Black Widow each in fighting crime on separate occasions. It was at this point that she becomes a radio show host under the name “Paige Angel.” She eventually realizes that she is too dependent on Matt and that her past is a constant barrier between them. Karen leaves Matt to accept a talk show host position in Los Angeles.
While in California, Karen has a routine blood test for an insurance policy that she is qualifying for. The supervillain Mysterio disguises himself as a doctor, performs the blood test, and tells her that she is HIV positive as part of his plan to destroy his nemeses before he himself dies of a brain tumour. Devastated, Karen returns to New York and tells Matt that she was HIV positive. Shortly afterwards, Mysterio contacts her in another disguise, who claims that she was stricken with the virus by a baby girl Daredevil is protecting; The baby, Mysterio claims, is the Antichrist. Karen initially tries to get Matt to give her the baby, but Matt realizes that she'd been contacted by his current foe (Although he didn't know who he was facing yet) and tells her not to blame an infant for her health. Karen runs off to a park to reflect on her past, and realizes that she has to be strong for Matt. She returns to find Daredevil being mercilessly beaten with his own baton by the assassin Bullseye, who has been sent to capture the infant. After attempting to fool Bullseye, Karen picks up a gun discarded by Bullseye and tries to shoot him. The gun is empty, but the act impresses Bullseye and he decides to let her live. While leaving the scene of the attack, Bullesye suddenly turns and hurls Daredevil’s baton at him. To protect Daredevil, Karen leaps in the way of the missile and it strikes her in her chest. She dies in Daredevil’s arms. She is the second love of Murdoch's life to be taken by Bullseye (though Elektra herself was ultimately resurrected)
Fan reactions remains split regarding her death, and some even believe her to still be alive considering the enemy Daredevil was facing was Mysterio, and anything done to her could be an illusion.
After her death, Mysterio taunts Daredevil, saying how baffled he is that Karen had not bothered to get a second opinion. After Mysterio's death, a conversation with Spider-Man leads Daredevil to realize that the infant he'd saved represented something positive that has come of the whole affair. He gives the baby up for adoption to a couple in New Jersey. Before he leaves, Matt named the baby after Karen, and hopes that her new parents would allow the occasional visit from her 'Uncle Matt'.