Manaudou won with a time of four minutes 05.34 seconds, setting a European record and becoming the first Frenchwoman to win an Olympic swimming title.
Pole Otylia Jedrzejczak finished second less than an hour after she was third in the 100 butterfly final while American Kaitlin Sandeno grabbed the bronze.
The 17-year-old was under world record pace for the first half of the race but slowed down over the final laps and held on to win the gold.
