The game is set in the Pacific theater of World War II, off the coast of the Midway Atoll. The goal is to attack the Japanese air fleet that bombed the American aircraft carrier, pursue all Japanese air and sea forces, fly through the 16 stages of play, and make their way to the Japanese battleship Yamato and destroy her. 11 of these stages consist of an air-to-sea battle (with a huge battleship or an aircraft carrier as the stage boss), while 5 stages consist of an all-aerial battle against a squadron of Japanese bombers with a mother bomber at the end.
In Sky Fighter 1943, players now have only one life, in the form of a large "fuel" meter; constantly depleting, but refillable by collecting various powerups (chiefly "Pow" icons).
Player has one special lightning attacks in exchange for some of the player's fuel.
Destroying a complete formation of red enemy planes will result in a power-up, such as a health boost or a new main weapon.