Mizuho was built to a similar design as the seaplane carrier Chitose, but with slightly less powerful diesel engines instead of Chitose's turbines. She carried 24 seaplanes, and was equipped to carry twelve miniature submarines, although she could not carry full loads of both at one time.
Mizuho participated in invasion support for much of her career; her first mission was with the Fourth Surprise Attack Force. On 1 March 1942, planes from Mizuho and Chitose damaged the American destroyerUSS Pope (DD-225), which was later sunk by aircraft from the aircraft carrier Ryujo and gunfire from the heavy cruisersAshigara and Myoko.
The American submarineUSS Drum (SS-228) torpedoed Mizuho at 23:03 hours on 1 May 1942 40 nautical miles (74 kilometres) off Omaezaki, Japan. She capsized and sank at 04:16 hours on 2 May 1942 with the loss of 101 lives. There were 472 survivors, of which 31 were wounded.