Mirra was born on April 4, 1974 in Chittenango, New York. He graduated from California State Polytechnic University, Pomona (Cal Poly Pomona).
In the 1990s, Mirra's brother, Tim, moved to Greenville, North Carolina, to attend East Carolina University. Dave moved to Greenville soon after. Fellow professional BMX rider Ryan Nyquist moved in with Tim. Mirra and Nyquist became quick friends and would build and ride ramps together. Greenville is now home to over twenty professional BMX riders. This gave Greenville the nickname "Protown" in the BMX community.
While still living in Chittenango, Mirra joined the Haro Bikes BMX team in 1987, at the age of 13. Video producers Plywood Hoods featured him in their videos in 1988. Mirra gained a sponsorship from Vision Street Wear in 1989. He was also sponsored by GT Bicycles through 1991, and then joined Hoffman Bikes in 1992 before re-signing with Haro in 1994.
Mirra turned professional in 1992. He won a medal at the X Games in every year from 1995 through 2009, with the exception of 2006. He won 24 medals at the X Games which stood as a record until 2013. He tied Tony Hawk and Joe Parsons as the fastest to reach 14 X Games medals. In 2005, Mirra won the Best Male Action Sports Athlete ESPY Award. His 14 gold medals are second-most to Shaun White. He retired from BMX riding in 2011.
From 2008 through 2013, Mirra competed in rallying and rallycross as a member of Subaru Rally Team USA. He had a career-best fourth-place finish during the 2013 Global RallyCross Championship. Mirra became interested in Ironman competitions, competing in his first triathlon in March 2013. He qualified for the 2014 Ironman 70.3 World Championship.
Mirra's success took him to numerous outlets besides riding his bike, such as hosting two seasons of MTV's Real World/Road Rules Challenge. He is featured in the Dave Mirra Freestyle BMX video game series and more recently appeared in the 2009 video game Colin McRae: Dirt 2. He published a photo-biography titled "Mirra Images", and was once one of People Magazine's "50 Hottest Bachelors". In the mid 2000s, Mirra signed an endorsement deal with DC Shoes. In 2007, Mirra started his own bike company, called MirraCo.
Mirra and his wife, Lauren, had two daughters. Mirra contracted bacterial meningitis in 2010. He recovered before resuming rallying.
On February 4, 2016, Mirra died from an apparent self-inflicted gunshot wound in Greenville, North Carolina. Authorities responded to a reported suicide and discovered his body in a truck. He had reportedly been visiting friends in the area. Allen Thomas, the mayor of Greenville, called Mirra "a great friend and wonderful human being". Mirra was 41 years old.
Mirra was posthumously diagnosed with chronic traumatic encephalopathy (CTE). In addition to the "countless" concussions he suffered during his career, his skull was fractured when he was hit by a car at 19 years old and he took up boxing after retirement. He became the first action sports star to be diagnosed with the neurodegenerative disease.