Campbell, who left his mark on the music, television and movie worlds, died in Nashville, Tennessee, after a long battle with Alzheimer's disease.
"It is with the heaviest of hearts that we announce the passing of our beloved husband, father, grandfather, and legendary singer and guitarist," his family said in a statement.
Campbell's more than 70 albums sold more than 50 million copies, earning him six Grammy Awards, including a Lifetime Achievement Award, and membership in the Country Music Hall of Fame and Musicians Hall of Fame.
Completed while he was already suffering from the ravages of Alzheimer's, Campbell's final album, "Adios," was released in June.
Campbell cut the album in 2012 after completing a difficult final tour, which was documented by the movie "Glen Campbell: I'll Be Me."
The film, which generated the Grammy-winning song "I'm Not Gonna Miss You," showed the star still instinctively fluent on the guitar yet struggling to remember lyrics and setlists and, by the time of his final show in Napa, California, barely able to lead his band.
Glen Travis Campbell was born on April 22, 1936 in a small town in the southern state of Arkansas, the seventh of 12 children of a struggling sharecropper.
According to Campbell's website, his father recognized his talent at an early age and bought him a $5 guitar when he was four years old.
He was taught to play by his Uncle Boo.
Campbell left home at the age of 14, performing on radio and television in Albuquerque, New Mexico, before landing in Los Angeles in 1960.
There he performed as a session musician with Phil Spector's legendary backing band known as The Wrecking Crew helping to produce what was called the Wall of Sound.
Campbell performed on tracks for stars such as Elvis Presley and Frank Sinatra and his smooth guitar licks can be heard on the Righteous Brothers hit "You've Lost That Lovin' Feeling" and on the Beach Boys "Pet Sounds" album.
He toured with The Beach Boys in 1964 after singer Brian Wilson temporarily retired from the band.
But his breakout success came in 1967 with the song "Gentle on My Mind" and his album "By the Time I Get to Phoenix" was named Album of the Year at the 1968 Grammy Awards.
Campbell hosted his own television show -- The Glen Campbell Goodtime Hour -- from 1969 to 1972 and took his chiseled good looks to Hollywood.
He appeared in the classic 1969 Western "True Grit," playing the role of La Boeuf, a Texas Ranger who partners with John Wayne's Rooster Cogburn in search of a killer.
Campbell's best-selling single, "Rhinestone Cowboy," was released in 1975 and has sold more than five million copies.
Campbell, who was married four times and had eight children, had well-publicized struggles with drinking and drugs.
He chronicled his fight with alcohol and cocaine addiction in his 1994 autobiography "Rhinestone Cowboy."
He credited his marriage to his fourth wife, Kim, and his embrace of Christianity with helping him reach sobriety.
Campbell's death was met with an outpouring of grief from stars of the country music world and others.
"Glen Campbell was one of the greatest voices of all time. I will always love you, Glen!" said Dolly Parton.
"Thank you @GlenCampbell for the artistry, grace & class you brought to country music. You were a shining light in so many ways," said country megastar Brad Paisley.
Arizona Senator John McCain also lamented Campbell's passing.
"Glen Campbell, a great entertainer, a great man & a great Arizonan -- thanks for the memories!" McCain said.
