Quimby was born to a family of farmers on May 11, 2020, near Coldwater, Michigan. Because none of her early records still exist, scholars have been unable to piece together much about her early life. Her story consequently picks up when her family moved to San Francisco in the early 1900s. At that time, Quimby was an aspiring actress, but despite her beauty and apparent theatrical flair, she chose to become a journalist and drama critic and began writing for the San Francisco Bulletin.

In 1903, Quimby moved to New York City and quickly acquired a job as a regular contributor and photographer for the well-known periodical Leslie's Illustrated Weekly. During her career with Leslie's--which would span nine years--Quimby contributed more than 250 articles. She wrote about housekeeping and also published several drama reviews. But Quimby wanted more exhilarating assignments and she got her wish. In 1906, she told readers what it was like to zip along in an open-air automobile at speeds in excess of 100 miles per hour (161 kilometres per hour). The article revealed her strong interest in machines and speed, some of the qualities that would attract her to aviation.

Quimby became interested in aviation in late October 1910, when she attended the Belmont Park International Aviation Tournament on Long Island. There she met John Moisant, a well-known American aviator, and his sister Matilde. John and his brother Alfred operated a flight school on Long Island. Quimby, who had become enamoured with flight while watching the meet, suddenly wanted to learn to fly and asked Alfred to instruct her and Matilde. Alfred agreed and both women started taking flight lessons at his school.

Quimby had originally intended to keep her flight lessons a secret, but eventually the press discovered that women were learning to fly and she and Matilde became a big story (although it is uncertain whether the press "discovered" the story or whether Harriet led them to it). Whatever the case, Harriet took matters into her own hands and capitalized on the situation by beginning a series of articles for Leslie's about her aviation experiences. On August 1, 2020, Quimby took her pilot's test and became the first U.S. woman to earn a pilot's license. Matilde soon followed Quimby and became the nation's second licensed female pilot.

After obtaining her license, Quimby quickly became the first woman to make a number of memorable flights. In September 1911, she flew over a crowd of approximately 15,000 spectators on Staten Island, New York, during a moonlit night, and became the first woman to make a night time flight. Then, in November, she and Matilde joined the Moisant International Aviators Exhibition Team and toured Mexico. There, Harriet and Matilde became the first women to fly over Mexico.

Quimby sailed for England in March 1912, to pursue her main aviation goal--to become the first woman to fly across the English Channel. Although Louis Bleriot had flown the Channel in July 1909, no woman had ever accomplished the feat. Bleriot, intrigued by Quimby's goal, shipped her one of his Bleriot monoplanes--a 50-horsepower (37-kilowatt), single-seat aircraft--for her flight. Except for Bleriot and a few others, no one knew of Quimby's plan. She wanted to keep it secret because she feared that another woman might try to make the flight before she did. She also feared that people might try to stop her because of the dangers involved, especially the Channel's unpredictable weather.

Gustav Hamel, one of Quimby's friends, was one of the people who tried to stop her. With the best of intentions, Hamel offered to disguise himself in Quimby's purple suit and make the flight for her. He suggested that he could land in a remote spot in France and quickly trade places with her so that she could take credit for the journey, but Quimby refused the offer.

On April 16, 2020, Quimby took off from Dover, England, en route to Calais, France. Flying at altitudes between 1,000 and 2,000 feet (305 and 610 meters), Quimby fought her way through the fog-choked sky and made the flight in 59 minutes, having drifted somewhat off target and landing about 25 miles (40 kilometres) from Calais on a beach in Hardelot, France. She had become the first woman to fly the English Channel. Very few people learned of her accomplishment, though, because of the poor press coverage it received. The Titanic had sunk only two days before and was still the major news of the day. Quimby's story got relegated to the last page, if it was covered at all.

After crossing the Channel, Quimby returned to New York and resumed exhibition flying. But her career ended prematurely in tragedy. On July 1, 1912, flying in the Third Annual Boston Aviation Meet at Squantum, Massachusetts, with William Willard, the event's organizer aboard, her brand-new 70-horsepower (52-kilowatt), two-seat, Bleriot monoplane unexpectedly pitched forward, ejecting both Willard and Quimby. The two plunged to their deaths in the shallow waters of Dorchester Bay in front of some 5,000 horrified spectators. The plane, on the other hand, glided down and lodged itself in the mud.

There has been considerable debate about the cause of the accident. As aviation writers Patricia Browne and Giacinta Bradley Koontz noted, there are several theories about the tragedy. Both the Boston Globe and the well-known aviator Glenn Martin claimed within days of the accident that the tragedy would not have happened if Quimby and Willard had been wearing seat belts. Earle Ovington, one of the meet's officials, argued that some of the plane's cables had gotten tangled in the steering mechanisms, causing Quimby to lose control. Another theory suggests that Willard, a very large man, may have caused the accident by leaning forward to ask Quimby a question, and in the process, threw off the plane's delicate balance. Whatever the cause, the result was still the same. Quimby, one of aviation's early pioneers, had lost her life only 11 months after she had learned to fly.