O'Brien was recruited by the Central Intelligence Agency during her senior year at Princeton University. After being divorced from three ex-husbands (all of whom were fellow CIA personnel), O'Brien went to prison because her third husband, Bill Rawlins, framed her of protecting a Taliban shipment of heroin. Later she worked with the CIA under Robert Bethell to capture the Punisher but the mission failed and she was back in jail. During the acquisition of the Punisher, O'Brien expressed sexual attraction to Castle and a desire to sleep with him.
Once in prison, she was routinely harassed by a gang of inmates, who were never able to beat her in a fight, so they framed her for the murder of a guard instead. O'Brien fled the prison and went to fellow former CIA agent William Roth for help. Once there she learned of the events surrounding Nicky Cavella's desecration of the Castle family graves, and that Bill Rawlins was in town. Deciding to kill her husband before she could make good on her escape, she caught him as he was about to shoot Castle with a sniper rifle, as he and Cavella were in league. She captured Rawlins and helped Castle by taking him to Roth's apartment.
She became pregnant after the night she finally slept with Castle and where they were attacked by Cavella's psychotic right-hand woman, Teresa Gazzera. After giving birth to Sarah, she gave the baby to her sister and traveled to the East and killed the Taliban leaders that had raped her over a decade prior. She met and worked with Castle again in Kabul. After getting rid of the Russian terrorists that were helped by Rawlins she accidentally stepped on a mine. She told Castle to accomplish her last wishes which were to exterminate the Taliban rapists and to kill Rawlins.
Normal human strength
- It is implied throughout the series that Kathryn is the same character as Kathryn McAllister, who appeared in Garth Ennis' Hitman series.
- Appearances of Kathryn O'Brien (Earth-200111)
- Minor Appearances of Kathryn O'Brien (Earth-200111)
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