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In a 2000 Entertainment Weekly review, Marc Bernadin complimented the show on its " spot-on pop-culture acumen " and " unparalleled sense of fun ", giving it a warm welcome from earlier " lame " superhero cartoons that he grew up with.

Peter Marks of The New York Times noted the show's use of adult humor and pop culture references, declaring it " the sort of playful satire that can appeal as much to a viewer of 37 as 7.

" Joly Herman of Commonsense media describes the show as a " cute, highly stylized series thrills the senses with its strange characters, funny situations, and lots of lowbrow humor " she goes on to say however, that the show does go from innocent to violent in no time and that there is not much protecting young viewers against the violent undertones.

Robert Lloyd of the LA Times said that the series might be " transgressive " based on the violence but " also cute ".

TV Guide chose The Powerpuff Girls as # 17 in a list of the 50 Greatest cartoon characters of all time.

The series has won two Primetime Emmys, two Annie Awards, and including those four wins, has been nominated a total of sixteen times for various awards.