DuPont died Wednesday in El Paso while in hospice care, Mary Skinner of VNA Hospice said. No other details were released.
She won 31 doubles and mixed doubles titles at three Grand Slams between 1941 and 1962. DuPont never played the Grand Slam tournament in Australia.
In 1967, five years after her last Grand Slam title, DuPont was inducted into the International Tennis Hall of Fame in Newport, R.I.
In a story last year in the El Paso Times, duPont spoke about her love of the game.
"It was always just tennis, tennis, tennis, tennis," she said. "I'm not sure why I loved the game so much. But I did. I just did. And I always have." DuPont played an aggressive game, serving and volleying, that suited her well for doubles. Her contemporaries included Pauline Betz, Doris Hart, Althea Gibson, Maria Bueno and Maureen Connolly.
DuPont won more titles at what is now the U.S. Open in singles, doubles, mixed doubles -- 25 -- than anyone else in history. She was recognized for the accomplishment in recent years with a gold ring from the governing body for U.S. tennis.
The El Paso paper, pointing to the website BleacherReport, wrote that duPont had spent 156 weeks ranked No. 1 in the world, tied with Connolly.
Born in Joseph, Ore., on March 4, 1918, duPont grew up on a ranch there. When the family moved to San Francisco, duPont played her first tennis on public courts in Golden Gate Park. Before long she was traveling the country.
Longtime friend and business partner Margaret Bloss, who lived with duPont in El Paso, said through her son that duPont's talent was spectacular.
"She was a super player, a super sport and a super friend," Leigh Bloss said.
In the early 1940s she met William duPont Jr., of the famous and prominent American family. The two married in 1947 and son Bill was born in 1952.
Her last Grand Slam title, mixed doubles at Wimbledon, came in 1962.
The couple divorced in 1964 and duPont moved to El Paso in 1966 where got became involved in the horse racing business with Bloss.
Billie Jean King said in a statement that duPont had a "huge impact" on her career.
"She was one of my she-roes and was a great influence on my life both on and off the court," King said. "I hope today's players and any boy or girl who dreams of a career in tennis will go to the history books and read about Margaret because her career wasn't just about winning matches, it was also about mentoring others."