Greene was born in Salinas, California, and developed an interest in music at an early age, starting with the piano. At 14, he began to play guitar and within a short time, was able to sit in with local bar bands. As he got older, he began composing his own songs. He recorded in a makeshift garage studio, burning his own CDs and selling them everywhere he could. Using the money he saved, Greene was eventually able to record and release his first full-length album, Rusty Nails, on his own.
After graduating from Oak Ridge High School in El Dorado Hills, California, Greene moved to Sacramento, where he began performing regularly. Marty DeAnda, owner of local label DIG Music, noticed Greene at an open-mic session in 2001 and signed him as the label's first artist. In late 2002, Greene released his first album with DIG, Gone Wanderin', which won the California Music Award for the Best Blues/Roots Album in 2003 and remained on the national Americana charts for over a year. In 2004, Greene released his third album, Sweet Somewhere Bound, and began receiving radio play for singles like "Honey I Been Thinking About You".
Greene has toured nationally with B.B. King, Phil Lesh, Ratdog, Huey Lewis, Susan Tedeschi, Taj Mahal, and Buddy Guy, and has played most major U.S. festivals, including All Good, Gathering of the Vibes, Mountain Jam, Newport Jazz, Newport Folk, South by Southwest, Wakarusa, Winnipeg Folk, Bonnaroo, Outside Lands, and Rothbury.
In early 2005, he signed with a major record label, Verve Forecast. Sweet Somewhere Bound was reissued that year, followed by a new release, American Myth, in March 2006. The following year, Greene joined Phil Lesh and Friends, the Grateful Dead bassist's ensemble dedicated to the interpretation of the Dead's extensive song book. Other members of the band at the time included John Molo, Larry Campbell and Steve Molitz. Also in 2005 his song "I Will Never Let Go" was used in the soundtrack for the movie Brokeback Mountain which was also released on the Verve label.
Meanwhile, Greene continued to pursue solo efforts, releasing Giving Up the Ghost on 429 Records in April 2008, and made his second visit to Late Night With Conan O'Brien in June 2008, performing "Like A Ball & Chain". Another song from the album, "I Don't Live in a Dream", was featured on episodes of the NBC television series Life in November 2008 and ABC's Private Practice in March 2009.
In October through November 2009, Jackie Greene played a series of shows with Gov't Mule, culminating at the end of the tour on Halloween at the Tower Theater in Philadelphia, during which Jackie played and sang through an entire set of Rolling Stones songs with Gov't Mule
