Before turning to drag racing, Kalitta competed in USAC events. He was the 1991 USAC Midget Series Rookie of the Year and went on to win the 1994 USAC Sprint Car championship. Across his open-wheel career he won 21 USAC events — 14 in midget races and seven in sprint car competition.
Kalitta made his NHRA debut at the 1998 Pomona season opener and immediately showed competitive pace. In his first season he received the Auto Club Road to the Future Award as the most promising newcomer. Over the following two decades he became one of the most formidable competitors in the Top Fuel class, accumulating runner-up finishes in the season standings in 2003, 2004, 2006, 2016, and 2019 — six runner-up finishes in total — before his first championship arrived.
Throughout this period he competed for Kalitta Motorsports, the team founded by his uncle Connie Kalitta, driving the Mac Tools-sponsored Top Fuel dragster. His crew chief from 2022 onwards has been Alan Johnson, a 14-time NHRA Top Fuel championship-winning tuner. Kalitta is the seventh driver to win a Top Fuel title with Johnson, who previously guided Gary Scelzi, Tony Schumacher, Larry Dixon, Del Worsham, Shawn Langdon, and Brittany Force to championships.
Kalitta entered the 2023 Countdown to the Championship sixth in the standings. He climbed through the playoff field with back-to-back wins at Reading and Charlotte before heading to the season finale at the In-N-Out Burger Pomona Dragstrip needing one more win. In a winner-take-all final round against Leah Pruett, Kalitta left the line first and recorded a 3.67-second pass to Pruett's 3.72, clinching his first NHRA Top Fuel world championship after 26 seasons of competition. En route to the title he defeated Dan Mercier, Josh Hart, Justin Ashley, and Leah Pruett in the final eliminations.
Kalitta entered the 2025 Countdown to the Championship as the No. 4 seed. His 2025 season included four race wins, three runner-up results, and eight No. 1 qualifiers. He won two races in the first four Playoff events, building a lead that proved decisive. The 2025 season was also notable because his Kalitta Motorsports teammate Shawn Langdon finished second in the standings, marking the first one-two finish in Kalitta Motorsports history and only the second time in NHRA history that a team swept the top two positions in the final Top Fuel standings.
As of the start of the 2026 season, Kalitta had 59 race wins, placing him fourth all-time in Top Fuel victories and 12th overall in NHRA history. He had recorded 66 career No. 1 qualifiers, tied for seventh all-time with Kenny Bernstein, and was seventh all-time in round wins with 839. His quickest elapsed time is 3.628 seconds, set at Seattle in 2025, and his fastest speed before 2026 was 341.34 mph at the same event. At the 2026 NHRA Four Wide Nationals at ZMax Dragway he set a new personal speed record of 342.98 mph. He maintained a streak of finishing every NHRA season in the top 10 in points across 28 seasons of competition.
Kalitta is the nephew of Connie Kalitta, the team owner, CEO of Kalitta Air, and a member of the Motorsports Hall of Fame of America. His cousin Scott Kalitta, a two-time NHRA Top Fuel champion, died in a racing accident on 21 June 2008. Both Doug and Scott were inducted into the Michigan Motor Sports Hall of Fame — Scott posthumously, Doug in 2011. Kalitta is married to Josie; their children include son Mitchell, who works on the team's finance side, and daughter Avery Ciorbu, a professional soccer player for Racing Louisville FC. He also owns Kalitta Charters, an air charter company providing cargo, passenger, and medical transport services, and on most race weekends he pilots the plane that carries his race team from Michigan to the venue.