Campbell is a native of Delight, Arkansas and began playing the guitar as a youth without ever learning to read music. By the time he was eighteen, Campbell was touring the south as part of the "Western Wranglers". In 1958, Campbell moved to Los Angeles to become a session musician.

Campbell's period as a session musician was successful, and he played with Bobby Darin, Rick Nelson, The Beach Boys (for which he was a touring member for a while in 1965), Merle Haggard, The Monkees, Elvis Presley, Frank Sinatra, Dean Martin, The Association, and The Mamas & the Papas, among others. His debut single was the moderate success "Turn Around, Look at Me." "Too Late to Worry — Too Blue to Cry" and "Kentucky Means Paradise" were similarly popular within only a small section of the country audience. By 1967, Campbell was ready to break through to the mainstream with "Gentle on My Mind" (written by John Hartford) and "I Wanna Live" in 1968 (see 1968 in music).

Campbell's biggest hits in 1968-1969 came on evocative songs written by Jimmy Webb: "By the Time I Get to Phoenix", "Wichita Lineman," "Where's The Playground Suzie?", and "Galveston". Campbell's voice and phrasing conveyed the songs' emotional content perfectly. The pair's tunefully sublime partnership is nicely chronicled on the 1974 album Reunion: The Songs of Jimmy Webb.

After he hosted a 1968 summer replacement for television's The Smothers Brothers Comedy Hour variety show, Campbell hosted his own weekly variety show, The Glen Campbell Goodtime Hour, from January 1969 through June 1972. At the height of his popularity, a 1970 biography by Freda Kramer, The Glen Campbell Story, was published.

During the early 1970s, Campbell released a long series of singles and appeared in the movies True Grit with John Wayne and Kim Darby and Norwood with Kim Darby and Joe Namath. In the mid-1970s, he had more big hits with "Rhinestone Cowboy", "Southern Nights", and "Sunflower".

Subsequently, Campbell began having trouble reaching the charts, and began to abuse drugs. By 1989, however, he had quit drugs and was regularly reaching the country Top Ten; songs like "She's Gone, Gone, Gone" were extremely popular. In the 1990s, Campbell mostly retired from recording, though he has not quit entirely. In 1994, his autobiography, Rhinestone Cowboy, was published.

Campbell returned to the charts in 2002 with a hit remake of "Rhinestone Cowboy" with UK dance producers Rikki & Daz. The song has also been covered by alternative group Radiohead.

Although for almost a decade, Campbell had professed his sobriety to fans at concerts and in his autobiography, he was embarrassed by a drunk driving arrest that included battery to a police officer in 2004. He was sentenced to ten days in jail, mostly due to the high level of intoxication.

In 2005, Campbell, the country music supergroup Alabama, and Grand Ole Opry pioneer DeFord Bailey, were inducted into the Country Music Hall of Fame.

Marriages include