Dore was born on July 26, 1965, into a Catholic family of twelve children on the southwest side of Chicago, Illinois of Polish and Irish descent. He started performing in 1989. Dore currently lives in Pasadena.

Dore has made many appearances on late-night television on shows such as ABC's Jimmy Kimmel Live!, CBS's The Late Late Show with Craig Kilborn, and NBC's Late Friday. He starred in a Comedy Central Presents half-hour special on April 9, 2004. He also starred in Comedy Central's "Citizen Jimmy" a one-hour stand-up special which was chosen "Best Of 2008" by iTunes. He was a writer–performer for the off-Broadway hit The Marijuana-Logues. He has also performed at the Montreal Comedy Festival, the U.S. Comedy Arts Festival, the Melbourne International Comedy Festival, the Amsterdam Comedy Festival, and for U.S. troops in Afghanistan. He had a role in the 2008 documentary film Super High Me.

He hosted the podcast Comedy And Everything Else with his wife Stefane Zamorano and previously with Todd Glass, who departed from the show in late 2009. In June 2009 he began producing The Jimmy Dore Show, a weekly one-hour comedic look at the news, which originates at KPFK 90.7 FM Los Angeles, airs nationally on the Pacifica Radio Network and online on TYT Network.

Dore wrote his first book, Your Country Is Just Not That Into You in 2014, and his latest comedy special, Sentenced to Live, was released on October 6, 2015. Much of his recent material is focused on the corporate news media, social criticism, and politics. He also hosts his monthly show, Left, Right & Ridiculous, at the Upright Citizens Brigade Theatre in Hollywood.

Since the 2016 presidential election, "Jimmy Dore has lit into Democrats for blaming hackers for their loss, raised doubts about the credibility of intelligence agencies, and seen the heavy hand of war hawks hyping the Russia connection to destabilize Europe and the Middle East," according to the Washington Post. Since Trump's inauguration, Dore "has zeroed in on corporate media and the hypocrisies of Democrats, rather than taking on Trump," according to Truthdig.