Blair competed for the United States in four Olympics, and in her Olympic career won five gold medals and one bronze medal.

At the 1988 Winter Olympics in Calgary, Alberta, Blair won the 500 meters and won a bronze in the 1000 meters. In the 500 meters race, Blair set a world record by completing the event in 39.10 seconds. She would win again at the 1992 Winter Olympics in Albertville, France in both the 500 and 1000 meters (1:21.90).

The 1994 Winter Olympics in Lillehammer, Norway were a coronation of sorts for Blair. She again won gold in the 500 meters (39.25) and 1000 (1:18.74) meters races, in dominating fashion. Blair finished .36 seconds ahead of the second best time in the 500 meters, and her 1.38 second margin in the 1000 meters race is the largest margin of victory in the history of the event. In the process she became the first American woman to win five gold medals.

After the 1994 Olympics, Blair continued to compete. In March of 1994, Blair set another world record in the 500 meters, becoming the first female to complete the race in under 39 seconds (38.99). On March 18, 1995, Blair skated in her last race, and went out as a champion. On that day, Blair set the American record in the 1000 meters (1:18.05).

Blair won several prestigious awards, including the 1992 Sullivan Award and Sports Illustrated Sportsperson of the Year, along with Johann Olav Koss, in 1994. She also was Female Athlete of the Year as selected by the Associated Press in 1994. Blair also won the World Cup points championship 11 times.

In 2004, she was elected to the United States Olympic Hall of Fame.