Duke made a successful transition to teen star playing vivacious twins on the cutesy, popular TV series "The Patty Duke Show" (ABC, 1963-66). But since her disastrous feature appearance in the dreadful cult classic "Valley of the Dolls" (1967) and the commercial failure of "Me, Natalie" (1969), she has mostly concentrated on TV roles, to which she seems more suited. Over her career, Duke has won two other Emmy Awards, as a runaway pregnant Southerner befriended by a black lawyer in the TV-movie "My Sweet Charlie" (NBC, 1970) and as the mentally unstable wife of Richard Jordan in the NBC miniseries "Captains and the Kings" (1976). She played a rather sensuous Martha Washington in both "George Washington" (CBS, 1984) and "George Washington II: The Forging of a Nation" (CBS, 1986). Duke brought her warm maternal presence to "Always Remember I Love You" (CBS, 1990) and garnered praise as real-life journalist Betty Rollin who struggled to assist her mother (played by Maureen Stapleton) to die with dignity in "Last Wish" (ABC, 1992). More recently, she was the mother of a Marine murdered by his trollop wife in "A Matter of Justice" (NBC, 1993) and an Amish woman who helps a detective find an arsonist in "Harvest of Fire" (CBS, 1996). In 1990, Duke co-produced and played herself in the small screen adaptation of her memoirs, "Call Me Anna" (ABC).

After her initial success with her own sitcom, Duke failed to find an appropriate follow-up. She was wife to Richard Crenna and mother of Helen Hunt and Anthony Edwards in "It Takes Two" (ABC, 1982-83) and the first female President of the United States in the short-lived "Hail to the Chief" (ABC, 1985). Duke also was a woman involved with a younger man in the summer sitcom "Karen's Song" (Fox, 1987) and was a woman who becomes a minister and moves to Idaho in "Amazing Grace" (NBC, 1995), which she also co-executive produced.

An unglamorous, earnest performer, Duke has most often played sensitive but troubled types who sometimes display an inner reserve of considerable strength but never lose their essential ordinariness. In her autobiography, she revealed details of her turbulent childhood and her victory over manic depression which she further chronicled in "A Brilliant Madness: Living With Manic-Depressive Illness". Considered one of the best female actors working in TV, Duke became only the second woman to be elected president of the Screen Actors Guild in 1985. (She resigned from the post in 1988.) During her 1973-82 marriage to actor John Astin, she was billed as Patty Duke Astin. Their two sons, Sean and Mackenzie, are both actors. As a producer on more recent projects, she has been variously billed as Anna Duke-Pearce and Anna Pearce.