DeJoria began her NHRA career in 2005, initially competing in the Super Gas category, before moving into a Super Comp dragster. Eight months after her NHRA debut, she went on to win the Sportsman Nationals in Fontana, California.

In 2009, DeJoria built her own racing team, Stealth Motorsports. At the 2011 NHRA Northwest Fall Nationals, she won her first ever NHRA national event win in TA/FC, becoming the second woman ever to do so. She co-owned and operated the team for three years, leaving in 2011 to join Kalitta Motorsports as their fourth member and second funny car driver. This move coincided with her transition to racing a nitro (Fuel) funny car at the 2011 Texas Fall Nationals.

In 2012, DeJoria raced her first final-round appearance at Bristol. That year she also set both a career best for time with a run of 4.032 and speed of 319.07 mph (513.49 km/h) at Reading.

In late 2012, DeJoria became engaged to American television personality and motorcycle customizer Jesse James. They married on March 24, 2013 at the estate of her father, entrepreneur John Paul DeJoria. On March 17, 2020, it was announced via social media that Alexis and Jesse James were getting divorced.

During the 2013 season, DeJoria had four semi-final finishes.

She played the role of Paula, in the 2013 movie “Snake and Mongoose”.

In 2014, DeJoria became the first woman ever to make a sub-four second pass, with a 3.997-second e.t., during the NHRA Winternationals at Pomona. At her next race in Phoenix, DeJoria won her first race in Funny Car. In March 2014, she picked up the second win of her professional career in Las Vegas. That May, she broke a Funny Car track record at Atlanta Dragway (4.012-second e.t.) while earning her the number one qualifier position. That summer, she went on to break Brainerd International Raceway’s Funny Car ET record with a 4.010-second pass, then reset her own record with a 3.998-second pass, the first sub-four second Funny Car pass at BIR. In September she won the U.S. Nationals in Indianapolis. On June 7, 2015, DeJoria reached the final round in Top Fuel Funny Car in the NHRA Summernationals at Englishtown.

DeJoria announced her return from a two-year hiatus in late 2019. She stated plans to run the entire 2020 schedule in the hopes of becoming the first woman to win a Funny Car championship. During this time DeJoria entered into a multi year sponsorship with ROKiT Phones and ABK Beer, with branding appearing on DeJoria’s vehicle, driver and crew uniforms, official merchandise and across her team’s transport fleet.