Comer's first major television credit was a guest appearance in a 1962 episode of My Three Sons titled "Heat Wave", followed by roles in several other dramatic series of the 1960s, such as Dr. Kildare and Bonanza. In 1964, she earned an Emmy nomination for Outstanding Performance in a Supporting Role by an Actress for her work on an episode on Arrest and Trial.
She made her film debut as the female lead in the 1964 comedy Quick, Before It Melts followed by a memorable role in the 1965 satire The Loved One, playing a seductive mortician who offers Robert Morse a choice for his uncle's funeral arrangements of "Inhumement, entombment, inurnment, immurement? Some people just lately have preferred ensarcophagusment."
Although Comer was cast opposite Michael Caine for Funeral in Berlin and appeared in publicity stills (she can be seen with Caine and Eva Renzi in a photograph on the DVD release), she had to be replaced because of illness. She had another leading role as a love interest of Marlon Brando and John Saxon in The Appaloosa (1966). The film, shot on location in Mexico, presented Anjanette as a Mexican peasant girl, a role she repeated in Guns for San Sebastian (1968). In between, she starred in Banning.
Comer's movie activity dropped off in 1970 after she played Ruth in the film version of John Updike's Rabbit, Run (1970). She later claimed she let her love life interfere with her work. Comer's later films include The Firechasers (1971) and Fire Sale (1977), and the TV movie The Long Summer of George Adams (1983).
