Franciscus was born in Clayton, Missouri, to Lorraine (née Grover) and John Allen Franciscus, who was killed in action during World War II. In 1957, Franciscus received a Bachelor of Arts degree in English and theatre arts from Yale University in New Haven, Connecticut, from which he graduated magna cum laude. He was a classmate of Dick Cavett and Bill Hinnant.
On March 28, 1960, Franciscus married Kathleen "Kitty" Wellman, the daughter of film Director william A. Wellman. They had four children — Jamie, Kellie, Korie, and Jolie. After his divorce from Kathleen, he married the former Carla Ankney in 1980. They were still married at the time of Franciscus' 1991 death (he was a four pack a day smoker) from emphysema in North Hollywood, California, at the age of 57.
His first major role was as Detective Jim Halloran in the half-hour version of ABC's The Naked City television series. Franciscus guest starred on the CBS military sitcom/drama Hennesey, starring Jackie Cooper, and on the NBC drama about family conflicts in the American Civil War entitled The Americans. CBS soon cast him in the lead in the 13-week series The Investigators, which aired from October 5 to December 28, 1961. He played the insurance investigator Russ Andrews, with James Philbrook as a co-star. Franciscus was also cast in the role of Tom Grover in the 1961 episode "The Empty Heart" of the CBS anthology series, The DuPont Show with June Allyson. He performed in many feature films and television programs throughout the 1960s and 1970s, preceded by a minor role in an episode of The Twilight Zone titled Judgment Night in 1959, and a major role in an episode of Alfred Hitchcock Presents: Summer Shade in 1961.