Peppard was born in Detroit, Michigan, as the son of an opera singer and a building contractor. He graduated from Dearborn High School in Dearborn, Michigan and served in the Marine Corps. He attended Purdue University (where he was studying Civil Engineering) and Carnegie Mellon University. He made his stage debut in 1949 at the Pittsburgh Playhouse then enrolled in the Actors Studio in New York and worked in summer stock. A Broadway appearance in "The Pleasure of His Company" in 1958 led to a MGM contract.
Peppard made his first television appearance, with a young Paul Newman, in an episode of The United States Steel Hour in 1956. A Broadway appearance in "The Pleasure of His Company" in 1958 led to a MGM contract. His good looks and elegant manner helped him receive his most famous film role as Paul Varjak in Breakfast at Tiffany's (1961) with Audrey Hepburn. This role made him a major film star lasting from the early to late 60's. However, he choose tough guys roles in big, ambitious pictures where he was somewhat overshadowed by ensemble casts. A drinking problem also started to effect his reputation.
After a string of B films in the early 70's Peppard moved to television. He had a leading role in the TV series Banacek (1972 - 1974), (part of the NBC Mystery Movie series of the 1970s), and played in Doctors' Hospital, in 1975, and in several other television films, which became in the later part of his career his major dedication.
He was married five times, and the father of three children.
A life long smoker Peppard was diagnosed with lung cancer in 1992. He died of pneumonia on May 8, 1994, at the age of 65. He is buried in Northview Cemetery in Dearborn, Michigan.