[1] Culp earned an international reputation for his role as Kelly Robinson on I Spy (1965–1968), the espionage television series in which he and co-star Bill Cosby played secret agents.

The pilot for Trackdown was "Badge of Honor", a 1956 episode of Dick Powell's Zane Grey Theatre, in which Culp starred as Gilman.

[7] After Trackdown ended in 1959 after two seasons, Culp continued to work in television, including a guest-starring role as Stewart Douglas in the 1960 episode "So Dim the Light" of CBS's anthology series The DuPont Show with June Allyson.

[9] He played Clay Horne in the series finale, "Cave-In", of the CBS Western Johnny Ringo, starring Don Durant.

In 1961, Culp played the part of Craig Kern, a morphine-addicted soldier, in the episode "Incident on Top of the World" in the CBS series Rawhide.

Some of his more memorable performances were in three episodes of the science-fiction anthology series on The Outer Limits (1963–1965), including the classic "Demon with a Glass Hand", written by Harlan Ellison.

In the series' episode "Hung High", he portrays an outlaw named Joe Costa, who attempts to frame Matt Dillon for lynching a prisoner who had killed the marshal's friend.

Culp then played perhaps his most memorable character, American secret agent Kelly Robinson, who operated undercover as a touring tennis professional, for three years on the hit NBC series I Spy (1965–1968), with co-star Bill Cosby.

In this, secret agent Maxwell Smart played by Don Adams in effect assumes Culp's Kelly Robinson character, as he pretends to be an international table-tennis champion.

The episode faithfully recreates the I Spy theme music, montage graphics, and back-and-forth banter between Robinson and Scott, with actor/comedian Stu Gilliam imitating Cosby.

[10] Culp co-starred in The Greatest American Hero as tough veteran FBI Special Agent Bill Maxwell, who teams up with a high-school teacher who receives superpowers from extraterrestrials.

[3] He reprised the role in the spin-off pilot The Greatest American Heroine and a voice-over on the stop-motion sketch comedy Robot Chicken.

In 1997, he played a CIA agent and the father of Dr. Jesse Travis on Diagnosis Murder along with Barbara Bain, Robert Vaughn, and Patrick Macnee.

Culp worked as an actor in many theatrical films,[11] beginning with three in 1963: As naval officer John F. Kennedy's good friend Ensign George Ross in PT 109, as legendary gunslinger Wild Bill Hickok in The Raiders, and as the debonair fiancé of Jane Fonda in Sunday in New York.

The video clip of "Guilty Conscience" features Culp as an erudite and detached narrator describing the scenes where Eminem and Dr. Dre rap lyrics against each other.

Culp was married five times:[5] to Elayne Carroll (1951–1956), Nancy Ashe (1957–1966), French actress France Nuyen, whom he met when she guest-starred on I Spy (1967–1970), Sheila Sullivan (1971–1976), and Candace Faulkner (from 1981).

He was also working on several screenplays, including an adaptation of the story of Terry and the Pirates that had already been accepted for filming and was scheduled to start production in Hong Kong in 2012, with Culp directing.