God of War III is expected to feature gameplay similar to that of previous installments. Some weapons include: the Zipper (fire bow), the trademark Blades of Athena, the Blade of Olympus, and the Cestus, a pair of fist gauntlets shaped like lion heads. This new weapon appears to have the ability to smash through solid objects such as rocks as well as a similar ability as the Blades of Athena. The Golden Fleece appears on Kratos' arm in gameplay trailers and the demo, and the Icarus' wings, showing that he keeps both from his adventure in God of War II.

In a recent screenshot, and in the demo, Kratos is seen tearing off the head of the God Helios. In the game his head can be used in a similar fashion to those of Medusa and Euryale from previous games. Although where their powers revolved around stone, Helios's stems from light. Its functions include blinding undead soldiers temporarily, as a lantern in dark areas and to find hidden rooms and passages.

Developers have stated that more weapons will be announced and will be more user-friendly than the sub-weapons from previous titles. Combos from previous titles will also make a return as well as new combos. The number of enemies onscreen has been increased to 50 as opposed to the maximum of 15 in previous God of War installments.

Game director Stig Asmussen claimed that the hardware capabilities of the PlayStation 3 would allow more flexibility in creating the characters of God of War III and to allow for further interaction with the environment. On March 26, 2009 a gameplay trailer was released at the Game Developers Conference. The trailer showed Kratos fighting a group of soldiers briefly and taking control of a cyclops to quickly dispatch the enemies, and ultimately killing the cyclops after the soldiers die. The trailer shown is gameplay from the E3 2009 demo.