The Argentina international deftly headed in Kevin De Bruyne's cross in the 34th minute, before converting a 63rd minute penalty to put City in command.
Newcastle rallied, with Jacob Murphy's first goal for the club four minutes later getting his side back in it, before City goalkeeper Ederson almost gifted the visitors a leveller but recovered well to deny Mohamed Diame.
However, Leroy Sane set up Aguero seven minutes from time for his and City's third, as the home side bounced back from defeat at Liverpool to restore their 12-point lead at the top of the standings after Manchester United had briefly cut it to nine earlier in the day. Newcastle remain 15th.