Blankers-Koen first achieved success as a teenager, winning a Dutch national championship in the 800-metre run in 1935; the next year, at age 17, she placed sixth in the high jump and competed in the 4 × 100-metre relay at the 1936 Olympics in Berlin. Her time of 11.0 sec in the 100-yard dash in Amsterdam in 1938 tied a world record. She married her coach, Jan Blankers, in 1940. In 1942 and 1943 she set world records in the 80-metre hurdles (11.0 sec), high jump (1.71 metres 【5.61 feet】), and long jump (6.25 metres 【20.51 feet】).

Prior to the 1948 Olympics in London, some experts thought Blankers-Koen was too old to be an Olympic sprint champion, and others denounced her for not attending to her duties as a wife and mother of two. Olympic rules limited Blankers-Koen to participating in only three individual events at the 1948 Games. Despite her jumping records, she preferred track events and made them her focus. She won the 100-metre sprint by a comfortable margin, but in the 80-metre hurdles she had to overcome both a slow start and a bumped hurdle in order to secure a narrow victory. Despite winning gold in her first two events, an emotionally spent Blankers-Koen was not confident going into the 200-metre event. Feeling both pressured to win and reviled for even participating, she burst into tears and told her husband that she wanted to withdraw. She reconsidered, however, and went on to win the final by a decisive margin, despite muddy conditions. In her last event, the 4 × 100 relay, she received the baton in fourth place and caught the lead runner at the finish line. Nicknamed the “Flying Housewife” by the press, Blankers-Koen received a hero's welcome when she returned to The Netherlands.

In 1951, after the pentathlon had been modified to consist of the shot put, high jump, 200-metre sprint, 80-metre hurdles, and long jump, Blankers-Koen set the first modern pentathlon record, with 4,692 points. She failed to earn a medal in her final Olympic appearance in Helsinki, Finland, in 1952. In 1999 she was named the top female athlete of the 20th century by the International Amateur Athletic Federation (IAAF; later called the International Association of Athletics Federations).