Early in the Pacific Campaign of World War II, Ōnishi was the head of the Naval Aviation Development Division in the Ministry of Munitions and was responsible for some of the technical details of the attack on Pearl Harbor in 1941 under the command of Admiral Isoroku Yamamoto.

While he is commonly credited with having devised the tactic of suicide air attacks (kamikaze) on Allied aircraft carriers, the project predated his tenure and was one that he had originally opposed as "heresy."

In a meeting at Mabalacat Airfield (known to the US military as Clark Air Base), near Manila on 19 October 1944, Ōnishi, who was visiting the 201st Navy Flying Corps headquarters, said, "In my opinion, there is only one way of assuring that our meager strength will be effective to a maximum degree.

[6] Ōnishi committed ritual suicide (seppuku) in his quarters on 16 August 1945 after the unconditional surrender of Japan at the end of World War II.

[7] Ōnishi's suicide note apologized to the approximately 4,000 pilots he had sent to their deaths, and he urged all young civilians who had survived the war to work towards rebuilding Japan and peace among nations.

Ōnishi's ashes were divided between two graves: one at the Zen temple of Sōji-ji in Tsurumi, Yokohama, and the other at the public cemetery in the former Ashida Village in Hyōgo Prefecture.