Booke was born in Buffalo, New York, a cousin of Max Yasgur. He earned degrees from both Columbia and Yale universities. He served in the United States Army during the Korean War as a counterintelligence officer.
Booke came to Hollywood via a theatre degree from Yale University and a decade on the New York Stage. One prominent early role was that of Senator Billboard T. Rawkins in the 1960 revival of Finian's Rainbow, a role foreshadowing his most famous character, that of Boss Hogg in The Dukes of Hazzard. During his early Hollywood acting career, Booke gained acclaim for notable supporting parts in noteworthy 1960s films such as Black Like Me, A Fine Madness, and Fail-Safe. In 1962, he was in Fiorello! and starred as the namesake's character.
In 1965, he guest starred as Sgt. Herschel Aronson in episode 19 "Faith, Hope, and Sergeant Aronson" of ABC's 12 O-Clock High military drama. He soon began focusing primarily on television roles in the 1970s and 1980s, and voice acting roles in the 1980s and early 1990s. Booke also once conducted the Buffalo Philharmonic Orchestra.
Booke earned an Emmy nomination for his appearance in Dr. Kildare in the episode "What's God to Julius?". He appeared in an episode of Mission: Impossible from the first season in 1966. Booke appeared in two early episodes of M*A*S*H, as General Barker in "Requiem for a Lightweight" and "Chief Surgeon Who?", the latter marked the debut of the character Corporal Klinger, with whom Booke's character had previously dealt.
He also had a recurring role in Norman Lear's groundbreaking sitcom All in the Family as Mr. Sanders, personnel manager at Archie Bunker's workplace, Prendergast Tool and Die Company. (He had previously appeared on All in the Family as Lyle Bennett, the manager of a local television station.) Booke was featured on an episode of Good Times, and had a recurring role as the Jewish mob boss "Lefkowitz" on Soap.
Booke's most notable role was in The Dukes of Hazzard as the humorously wicked antagonist to Bo and Luke Duke. The series ran on CBS for seven seasons, from 1979 to 1985 and spawned an animated series, The Dukes (1983), two reunion TV specials (by which time Booke had died, and the character of Boss Hogg was also said to be deceased), a feature film (2005) and The Dukes of Hazzard: The Beginning (a 2007 TV movie).
Booke had stopped appearing physically in acting roles, but he continued to perform voice work on several television shows and movies, occasionally as narrator, and sometimes as a cartoon character's voice, in such movies as Scooby-Doo Meets the Boo Brothers (1987 TV movie), Gravedale High (1990 television series), and Rock-A-Doodle (1991).
Booke was married to Miranda Knickerbocker (the daughter of Hubert Renfro Knickerbocker) from 1958 to 1973. They had two children, Alexandra and Nicholas. Booke has a brother, Fred.
On February 11, 1994, Booke died of colorectal cancer in Sherman Oaks, California. He is interred at the Hillside Memorial Park Cemetery in Culver City, California. His tombstone reads, "Beloved Pa, Grandpa, Brother and Boss."Gone are the Days! (1963) as Ol' Cap', Stonewall Jackson Cotchipee
Black Like Me (1964) as Dr. Jackson
Les Félins (1964) as Harry
Fail-Safe (1964) as Congressman Raskob
A Fine Madness (1966) as Leonard Tupperman
Up the Down Staircase (1967) as Dr. Bester
Matchless (1967) as Colonel Coolpepper
Bye Bye Braverman (1968) as Holly Levine
What's Up, Doc? (1972) as Harry
Slaughterhouse-Five (1972) as Lionel Merble
The Iceman Cometh (1973) as Hugo Kalmar
The Take (1974) as Oscar
Devil Times Five (1974) as Harvey Beckman
Bank Shot (1974) as Al G. Karp
The Manchu Eagle Murder Caper Mystery (1975) as Dr. Melon
Mastermind (1976) as Max Engstrom
Special Delivery (1976) as Hubert Zane
Freaky Friday (1976) as Mr. Dilk
The Other Side of Midnight (1977) as Lanchon
Record City (1978) as Coznowski
The Cat from Outer Space (1978) as Presiding Judge (uncredited)
Rock-A-Doodle (1991) as Pinky - The Manager (voice)
The Sleeping Prince (1956)
Nature's Way (1957)
Heartbreak House (1959)
Fiorello! (1959–61) (replacement)
Finian's Rainbow (1960)
Purlie Victorious (1961–62)
The White House (1964)
The Iceman Cometh (1966)
Come Live with Me (1967)
Morning, Noon and Night (1968)