At the time of his death, Hootkins was planning a screenplay on Fatty Arbuckle, focusing on the comic's life after his fall from grace in 1921; he had met Arbuckle's last wife, Addie McPhail.

He also appeared in several roles on television, including Charles Frohman in The Lost Boys (1978), Colonel Cobb in the remake of The Tomorrow People and as Uncle George in the 2002 remake of The Magnificent Ambersons.

Hootkins appeared in many roles that made him a welcome figure at fan conventions, particularly for Star Wars in his role of Jek Tono Porkins. He also appeared in significant parts in films as Hardware (1990), Like Father, Like Santa (as Santa Claus), and Hear My Song (1991), where he was the Mr. X who was presumed to be the Irish tenor Josef Locke under a false name. He portrayed Fatty Arbuckle in Ken Russell's infamous 1977 flop Valentino, and played Hans Zarkov's assistant in the 1980 Flash Gordon. He also made appearances in such films as Raiders of the Lost Ark and Tim Burton's Batman (the latter as Lt. Eckhardt).

In England, Hootkins found work in the theatre as well as in film, and he would have his greatest success on stage portraying Alfred Hitchcock in Terry Johnson's 2003 hit play Hitchcock Blonde, first at the Royal Court Theatre and in London's West End. The role was such a success that producers planned to take the show to Broadway, but it was canceled after he was diagnosed with cancer.

Hootkins died of pancreatic cancer in Santa Monica, California on October 23, 2005, at the age of 57. His mausoleum is at Sparkman-Hillcrest Memorial Park Cemetery.

Hootkins attended Princeton University, studying astrophysics before transferring to oriental studies, where he became fluent in Mandarin Chinese. This stood him in good stead when he played the part of an interpreter in an episode of The West Wing titled "Impact Winter". He was a mainstay of the Theatre Intime, making a particular impact with his performance in Orson Welles' Moby Dick—Rehearsed. On the recommendation of his friend John Lithgow, he moved to London in the early 1970s and trained as an actor at the London Academy of Music and Dramatic Art (LAMDA). He made his home in London until 2002, when he moved to Los Angeles.