The Pro Evolution Soccer series is renowned for its realism, and Pro Evolution Soccer 6 is abundant with new gameplay additions. Player AI has been massively upgraded, with players running intelligently into space when not in possession of the ball and pointing where they want the pass placed to continue the attack. Similarly, the physical side of play has been refined, with players working to turn a defender as they receive the ball, while defenders must learn to stand off slightly to prevent such moves.

Series creator Shingo 'Seabass' Takatsuka has also worked to refine the shooting system of the new game, and players will be able to attempt more snap shots than in previous versions, while volleys and half-volleys have been redesigned. Other new moves include the ability to retain control of the ball when sliding in to tackle, while all-new feints and backwards dribbling are now available thanks to the improved dribbling controls, while headers have been changed to allow players more movement in the way their strikers jump and head the ball.