Flynn was born Lawrence Matthew Cardine in Oakland, California. Flynn cited Black Sabbath as his biggest influence and the reason he plays guitar. Other influences include Bay Area thrash metal bands like Exodus, Metallica, Slayer and hardcore punk/crossover thrash groups such as Dead Kennedys, DRI, and Suicidal Tendencies.

Flynn joined the thrash metal band Forbidden (originally Forbidden Evil), while in his graduating year at American High School. He played in this band from 1985 to 1987. He wrote four songs which appeared on their debut album, « Chalice of Blood », « Forbidden Evil », « As Good As Dead », and part of « March into Fire », but left before an album was released to join local thrash metal rivals Vio-lence, alongside ex-Machine Head guitarist Phil Demmel. Flynn then went on to form Machine Head, whose debut album Burn My Eyes made Flynn a rising metal star.

In January 2005, he was selected as one of the four team captains of Roadrunner United, an act to celebrate the 25th anniversary of Roadrunner Records. Flynn wrote, produced and recorded guitar on four songs, these were The Rich Man, Independent (Voice of the Voiceless), Army of the Sun and The Dagger and on the latter he sang and wrote lyrics alongside Howard Jones of Killswitch Engage.
Machine Head’s album The Blackening (2007) climbed to number 54 on the US Billboard after appearing on the charts only two weeks previously; it was also nominated for a Grammy Award, making it by far the band’s most successful album. On June 11, 2007, Flynn received the Metal Hammer 2007 Golden God Award. In honor of Debbie Abono and Ronnie James Dio, Flynn recorded and released for free online a cover of Black Sabbath’s « Die Young ». Abono managed Flynn and Phil Demmel when they were members of Vio-lence.

In December 2013, Flynn and fellow Machine Head guitarist Phil Demmel collaborated with online education site JamPlay.com to put together a series of guitar lessons for aspiring guitarists and members of JamPlay.
Flynn had a break-in at his house in which several items, including guitars, were stolen. One guitar, the Washburn 333 or « Dimebolt », was given to him by Dimebag Darrell.[9] In 2016, the « Dimebolt » guitar was returned to Flynn. Machine Head debuted at number 22 on the Billboard 200 chart, with Unto the Locust the band’s highest performance. They also debuted at number 5 on the German music chart. The album has sold over 100,000 copies in the United States.