Born Shirley Ann Roque in Burlington, Vermont, Muldowney began street racing in the 1950s in Schenectady, New York. "School had no appeal to me. All I wanted was to race up and down the streets in a hot rod," declared Muldowney. When she was 16, she married 19-year-old Jack Muldowney, who would build her first dragster.
It was Jack Muldowney who first taught me how to drive a car. Jack was the mechanic. He was the guy who tuned the cars that let the girl beat all the boys. I was a kid from upstate New York with no guidance, no direction. I was headed for trouble, nothing going for me. Then I found the sport at a very young age and was able to make something out of it.
In 1958, Muldowney made her debut on the dragstrip of the Fonda Speedway. She obtained her NHRA pro license in 1965. She competed in the 1969 and 1970 U.S. Nationals in a twin-engine dragster in Top Gas. With Top Gas losing popularity, Muldowney switched to Funny Car, buying her first car from Connie Kalitta.
Around this time, she and her husband drifted apart; they finally divorced in 1972. "He didn't want to go nitro racing and we parted, but we stayed friends all those years until he passed away [in 2007]," she later said.
Muldowney won her first major event, the International Hot Rod Association (IHRA) Southern Nationals, in 1971.
She stepped up to Top Fuel, getting her license in 1973. From 1973 to 1977, she teamed up with Connie Kalitta as the Bounty Hunter and Bounty Huntress in match races, in a pair of Ford Mustangs, hers a Buttera chassis, his a Logghe. The Bounty Huntress Mustang caught fire at Dragway 42 in Ohio in 1973.
An unprecedented three NHRA Top Fuel Dragster world championships followed, in 1977, 1980, and 1982.
Muldowney success met enormous opposition from those who felt drag racing (or any form of motorsport, for that matter) was no place for women. Don Garlits has said about her:
Now, if you ask who do I have the most respect for, I'd say Shirley Muldowney. She went against all odds. They didn't want her to race Top Fuel, the association, the racers, nobody...Just Shirley.
Muldowney noted, "NHRA fought me every inch of the way, but when they saw how a girl could fill the stands; they saw I was good for the sport."
A crash in 1984 crushed her hands, pelvis, and legs, necessitating half a dozen operations and 18 months of therapy. Muldowney was sidelined for a long period, but returned to the circuit in the late 1980s. She continued to race, mostly without major sponsorship, throughout the 1990s in IHRA competition as well as match-racing events. She returned to the NHRA towards the end of her career, running select events until her retirement at the end of 2003.
Muldowney was described by longtime drag racer Fred Farndon as the "best 'natural' driver (top fuel or funny car), no question."
Recent activities include the dictation of her memoirs, Shirley Muldowney's Tales from the Track, which Bill Stephens transcribed, and which Sports Publishing L.L.C. published in 2005.
In March 2016 Muldowney disregarded a cancer scare to be the official starter of the Amalie Oil NHRA Gatornationals. Having been given a diagnosis of lung cancer prior to the event, Muldowney was later given a diagnosis of histoplasmosis, a curable and non-malignant fungal infection which can mimic cancer.
Muldowney operates a charitable organization, Shirley's Kids, which helps children in need in cities where drag racing is part of the community.In 1975, she was voted the first woman member of the ten-person Auto Racing All-American team by the American Auto Racing Writers and Broadcasters Association.
In 1976, she was named Drag News Top Fuel Driver of the Year and voted to the Auto Racing All-American Team for the second time.
In 1977, she won the NHRA Winston world points championship, becoming the first woman to claim drag racing's most prestigious title. Recipient of "Outstanding Achievement Award" from the United States House of Representatives on October 14, 1977. Named Drag News Top Fuel Driver of the Year for the second straight season. Named Car Craft Magazine Person of the Year during the annual Car Craft Awards Banquet, Indianapolis, Indiana. First Top Fuel driver to win three NHRA national events back-to-back.
1980 Won NHRA Winston world points championship for the second time.
1981 Won AHRA world championship. Voted to Auto Racing All-American team for the fifth time. Voted Car Craft Magazine All-Star Team, Top Fuel Driver of the Year, for the second year in a row.
1982 Won NHRA Winston points championship, becoming the first person to claim drag racing's most prestigious title three times. Voted to Auto Racing All-American Team for the fifth time.
In 1990, she was inducted into the Motorsports Hall of Fame of America.
In 2001, she was ranked number 5 on the National Hot Rod Association's 50th Anniversary list of its Top 50 Drivers, 1951-2000.
In 2004, she was inducted into the International Motorsports Hall of Fame.
In 2005, she was inducted into the Automotive Hall of Fame.
in 2008, ESPN ranked her 21st on its list of the Top 25 Drivers of All Time, citing her record as the first woman to win a major racing championship.