[9] O’Keefe played the lead role in the 1982 film Split Image as a college athlete who is lured into a religious cult by a beautiful girl (Karen Allen).
[10] He appeared in the Neil Simon movie The Slugger's Wife (1985) as Darryl Palmer, a baseball player for the Atlanta Braves who enjoys the fame and fringe benefits of bachelor life until he meets rock singer Debby Huston, falls in love, and decides to settle down.
He appeared in the thriller film The Glass House and starred with Tommy Lee Jones in the 1983 pirate adventure Savage Islands.
O'Keefe's Broadway theatre credits include Side Man (1998),[11] Mass Appeal (1981),[12] Fifth of July (1980),[13] and Reckless with Mary-Louise Parker (2004).
[15] O'Keefe's highest-profile television role was as Fred, the husband of Jackie Harris (Laurie Metcalf) on the ABC series Roseanne from 1993 to 1995.
[18] In 2014, he appeared in a recurring role in Homeland as CIA agent and former interim station chief John Redmond [19] and as Detective Winslow in the Amazon Prime original TV series Sneaky Pete.