He was born Victor Charles Buono in San Diego, California, a son of Victor Francis Buono (May 28, 1907-May 17, 1981) and Myrtle Belle Keller (October 19, 1909 -August 27, 1979).

His maternal grandmother, Myrtle Glied (April 18, 1886-December 9, 1969), had been a Vaudeville performer on the Orpheum Circuit. When he was a little boy, she taught him songs and recitations and encouraged him to perform for visitors.

Even though the young Buono enjoyed the polite applause of those captive audiences, he thought he wanted to be a doctor. When he was sixteen, Father John Aherne of the St. Augustine High School in San Diego cast him as Papa Barrett in the play The Barretts of Wimpole Street. Buono appeared in three plays a year while attending high school, which included Aladdin and His Wonderful Lamp and Shakespearean dramas. He even played the title role of Hamlet.

He soon forgot about having a medical career. He started appearing on local radio and television stations, and at the age of eighteen he joined the Globe Theater Players in San Diego. The director had confidence in Buono and cast him in Volpone, Midsummer Night's Dream and other Globe presentations. He received good notices for his various Shakespearean roles and in modern plays such as The Man Who Came To Dinner and Witness For The Prosecution.

In the summer of 1959, a talent scout from Warner Bros. saw the heavyset Buono play Falstaff at the Globe and took him up to Hollywood for a screen test. He made his first network TV appearance playing the bearded poet Bongo Benny in an episode of 77 Sunset Strip. Over the next few years he appeared on numerous shows playing menacing heavies in just about every Grade "A" private eye series. He also appeared on The Untouchables.

Because of his overweight stature, Buono usually played older characters. After appearing in a few motion pictures uncredited, he was cast by director Robert Aldrich in the psychological horror movie What Ever Happened to Baby Jane? (1962) with screen luminaries Bette Davis and Joan Crawford. He played the part of the ne'er-do-well musical accompanist, Edwin Flagg.

Victor Buono was nominated for an Academy Award for Best Actor in a Supporting Role for his performance in What Ever Happened to Baby Jane?

He appeared in Hush, Hush, Sweet Charlotte (1964) playing Big Sam Hollis, the father of Bette Davis, who had the title role, which was also directed by Aldrich. And he appeared in The Greatest Story Ever Told (1965) starring Max von Sydow, Michael Anderson, Jr. and Carroll Baker, which was produced and directed by George Stevens. Buono played the role of the High Priest Sorak in this story about Jesus.

He also appeared in such movies as 4 for Texas (1963), Robin and the Seven Hoods (1964), The Silencers (1966), Who's Minding the Mint? (1967), Target: Harry (1969) and Beneath the Planet of the Apes (1970).

Buono had a vast body of work in movies, and among his extensive TV appearances were the recurring roles of the demented Count Manzeppi on the popular (CBS) series The Wild Wild West starring Robert Conrad and Ross Martin, which ran from 1965 to 1969, and he also played an unrelated character in the second and final Wild Wild West reunion movie. He played King Tut on the (ABC) series Batman with Adam West and Burt Ward, which ran from 1966 to 1968. He was in demand to play villains of various nationalities and ethnic origins on many programs between 1964 and 1970.

His later roles were more of pompous intellectuals and shady con men. He could also play straight roles. In the TV miniseries Backstairs at the White House (1979) he portrayed President Taft and delivered a poignant tribute to the late Mrs. Taft.

Buono liked to read and write, and one of his main hobbies was Shakespeare. "The more you study him," he said, "the greater he grows."

Victor Buono died of a heart attack at his ranch in Apple Valley, California.