In 1968, O'Keefe was a member of a four-man heavy psychedelic rock band named Calliope. The group recorded one album, Steamed, for Buddah Records before disbanding.

O'Keefe is best known for the hit single, "Good Time Charlie's Got the Blues", which was released in September 1972, and reached number 9 on the U.S. Billboard Hot 100 chart, and for "The Road", covered by Jackson Browne on Running on Empty. "Good Time Charlie's Got the Blues" stayed on the Billboard chart for 14 weeks and sold a million copies. Sales culminated in a gold disc issued by the R.I.A.A. in June 1973. The song became O'Keefe's only song to reach the Australian top 100, peaking at number 53 in February 1973.

O'Keefe's songs have been covered by numerous musicians, including Jackson Browne ("The Road"), Gary Stewart ("Quits"), Elvis Presley, Glen Campbell ("Quits"), John Denver ("Along For The Ride"), Donny Hathaway ("Magdalena"), Leo Sayer ("Magdalena"), Jerry Lee Lewis, Judy Collins ("Angel Spread Your Wings"), Leon Russell, Willie Nelson, Waylon Jennings, Jimmy Buffett, Alison Krauss, Ben Harper, Cab Calloway, Mark-Almond, Andy Williams, and Dwight Yoakam ("Under the Covers"). In Italy his song "The Road" has been covered by Ron, with Italian lyrics written by Lucio Dalla (and re-titled "Una città per cantare").

In 2020, O'Keefe released "Looking Glass & The Dreamers"

1971 - Danny O'Keefe Cotillion Records
Produced by Ahmet Ertegun

1972 - O'Keefe - Signpost/Atlantic
Produced by Arif Mardin
Contains the top-ten hit "Goodtime Charlie's Got the Blues"

1973 - Breezy Stories - Atlantic Records
Produced by Arif Mardin
Contains the single "Angel Spread Your Wings"

1975 - So Long Harry Truman - Atlantic Records
Produced by John Boylan
Contained the single "Quits"

1977 - American Roulette - Warner Bros. Records
Produced by John Court and Kenny Vance

1979 - The Global Blues - Warner Bros. Records
Produced by Jay Lewis and Danny O'Keefe

1984 - The Day To Day - Coldwater Records
Produced by Mathew McCauley and Tony Peluso
Contained the singles "Along for the Ride" and "Someday"
Both singles charted in the "20's" in AC charts

1989 - Redux - Beachwood/Chameleon Records
(this is a re-release of The Day To Day with a new title and two new songs)
Contained the singles "Along for the Ride" and "Someday"
Both singles charted on AOR charts in the 20's
VH1 played the video of "Along for the Ride"

1999 - Runnin' From the Devil - Bicameral Songs
January 25th, 2000

2003 - Don't Ask w/Bill Braun - Bicameral Songs
Produced by Bill Braun
All songs written and performed by Danny O'Keefe and Bill Braun

2004 - Classics - Rhino Handmade Records
Compilation of songs from Danny O'Keefe's first 6 albums

2008 - In Time - Bicameral Songs
Produced By Mick Conley
All songs written/co-written and performed by Danny O'Keefe

2015 - Light Leaves the West - Road Canon Music, LLC
Produced By Garey Shelton
All songs written/co-written and performed by Danny O'Keefe

2017 - Home - Road Canon Music, LLC
Produced By Garey Shelton
All songs written/co-written and performed by Danny O'Keefe

2020 - Looking Glass & The Dreamers - Road Canon Music, LLC
Produced by Danny O'Keefe