The deposed champions got the goals through David Villa, Fernando Torres and Juan Mata at Arena da Baixada in Curitiba.
Netherlands ended top of Group B with nine points as they defeated Chile 2-0 in a simultaneous fixture, with both countries advancing to the last-16 of the competition.
Spain and Australia - whose first-round exit was confirmed prior to their meeting - were evenly matched for much of the opening half.
However, Vincent del Bosque's men took the lead nine minutes before the break, as record scorer Villa netted with a cute back-heel flick off a right-wing cross by Juanfran. It was Villa's 59th international goal.
La Roja improved as the game matured, and doubled their advantage in the 69th minute, as Chelsea striker Torres calmly finished in the box after being released by Andres Iniesta.
Substitute Mata, on for Villa, put the result beyond doubt in the 82nd minute when he rolled the ball between the legs of goalkeeper Mat Ryan from close range.