Farentino made his film debut in the forgotten thriller "Psychomania/Violent Midnight" (1963) and next appeared in "Ensign Pulver" (1964) before catching a break with the lead in 1966's "The Pad...(And How to Use It)", as the hip friend of Brian Bedford giving him advice on how to be a swinger. Farentino stole the movie and earned a Golden Globe Award as the most promising newcomer, but as the late 60s were a difficult time for conventional leading men, the actor found good roles were sparse. After appearing in the ensemble melodrama "Banning" (1967) and opposite Patty Duke in "Me, Natalie" (1969), Farentino found himself mostly confined to TV work for much of the 70s and 80s. When he found the occasional film role, it was usually as men of power like the Navy commander from the past in "The Final Countdown" (1980) and the district attorney and adversary to Tom Selleck in "Her Alibi" (1989). More recently, he was a police captain in the lame comedy "Bulletproof" (1991).

The small screen has afforded him better opportunities, beginning with his regular role as the novice and most unorthodox attorneys in the NBC series "The Lawyers" (1969-72), which aired under the umbrella of "The Bold Ones". He returned to series work as a CIA agent turned private investigator in "Cool Million" (NBC, 1972-73). It was almost a decade before the actor returned to the weekly grind when he appeared as the mysterious Dr. Nick Toscanni during the 1981-82 season on "Dynasty" (ABC). In 1984, Farentino played the human lead to a police helicopter on the short-lived "Blue Thunder" (ABC) before trying a romantic role as the newsroom boss and love interest of Mary Tyler Moore on "Mary" (CBS). The actor was teamed romantically with another female icon--Julie Andrews--in her short-lived ABC sitcom "Julie" (1992). For his portrayal of Simon Peter in the 1977 NBC miniseries "Jesus of Nazareth" he earned an Emmy nomination. More often, he was paired with strong females like Joan Collins in the 1986 CBS miniseries "Sins" and as Juan Peron to Faye Dunaway's "Evita Peron" (NBC, 1981). Farentino portrayed Boston Mayor Kevin White in "Common Ground", the 1990 CBS miniseries about school busing in Boston, and played an abusive husband opposite his real-life ex-wife Michele Lee in "When No One Would Listen" (CBS, 1992). More recently, Farentino played the doomed Jose Menendez in the 1994 Fox miniseries "Honor Thy Father and Mother: The True Story of the Menendez Murder".