The Best of The Byrds: Greatest Hits, Volume II was released just prior to the highly publicized reunion of the five original members of the Byrds. The album was compiled with input from the band's guitarist and leader Roger McGuinn, although rock historian Christopher Hjort has suggested that it offered a somewhat erratic survey of the band's later years.

The bulk of the album's songs are drawn from the years 1969 through to 1971, with the 1968 albums The Notorious Byrd Brothers and Sweetheart of the Rodeo only being represented by "Wasn't Born to Follow" and "You Ain't Goin' Nowhere" respectively. The album also included "He Was a Friend of Mine", which had originally appeared on 1965's Turn! Turn! Turn! album, a period already covered by the band's first compilation album, The Byrds' Greatest Hits. The album featured a number of the band's U.S. charting singles, including "Ballad of Easy Rider" (number 65), "Jesus Is Just Alright" (number 97), "Chestnut Mare" (number 121), and "You Ain't Goin' Nowhere" (number 74). However, since none of these singles reached the U.S. Top 40, they couldn't really be considered bona fide hits.