Greatest Hits was created by Geffen shortly after the band's February 2005 breakup, termed an "indefinite hiatus" by the label.

Andy Greenwald of Blender called it a "flawless compilation," covering the group's transition from "nudists to near-geniuses.

By 2004, Blink-182, consisting of guitarist Tom DeLonge, bassist Mark Hoppus and drummer Travis Barker, had emerged as the biggest pop-punk act of the era, releasing the seven-times-multiplatinum Enema of the State (1999) and number one album Take Off Your Pants and Jacket (2001).

[3] The band had taken a brief break in 2001 when DeLonge suffered a herniated disc in his back,[4] during which time he recorded an album—titled Box Car Racer—which contained darker musical material he felt unsuited for Blink.

[5] The moody subject matter and music on Box Car Racer edged its way into Blink's sound as well on their next effort, an eponymous fifth studio album (2003).

[9] DeLonge became increasingly conflicted both about his creative freedom within the group and the toll touring was taking on his family life.

[12] Following the 2004 Indian Ocean earthquake, DeLonge agreed to perform at Music for Relief's Concert for South Asia, a benefit show to aid victims.

Further arguments ensued during band rehearsals:[13] DeLonge asserted he would only record another album at his home in San Diego, suggesting he email Pro Tools files to Hoppus and Barker in Los Angeles.

"[14]: 150–51  DeLonge quit the band, coming to the conclusion that the trio had simply grown apart as they aged, had families, and gained fame.

[16]: 10  It has been described by journalist Joe Shooman as "a satisfyingly fast-assed punk song in the vein of NOFX with some very adept dynamic breakdowns."

"[16]: 42  The distinctive riff of "Dammit" was created when Hoppus was forced to skip over the missing two strings on an acoustic guitar.

[16]: 70  It reached number 11 on Billboard's Hot Modern Rock Tracks chart in 1998, and received heavy radio airplay.

[20] "Adam's Song," the piano-laced seventh track of the compilation, was written primarily based on the loneliness that Hoppus experienced during unending days of touring in 1997–98.

"[29] "Not Now", a B-side from the band's 2003 album and first included on this compilation, features a church organ in its verses and guitar riffs reminiscent of the Descendents; its subject matter continues the theme of complicated miscommunication and fading love.

[35] In the United States, Greatest Hits peaked at number six on both the Billboard 200 and the magazine's Top Internet Albums chart, selling 72,000 copies in its first week.