The Argentine, who scored a late goal to give City the title with a win over QPR last year, netted in the 78th minute to allow his side a 2-1 victory to make it two in a row at United in the league.
James Milner opened the scoring for the visitors seven minutes into the second half when he was teed up by Samir Nasri before firing a left-footed effort past David de Gea with the help of a slight deflection.
Seven minutes later, United were back on level terms when City skipper Vincent Kompany inadvertently put the ball into the back of Joe Hart's net after Robin van Persie's free-kick was met with a miscued header from Phil Jones which struck the Belgian and went in.
However, with 12 minutes remaining, Aguero climbed off the subs bench and produced a dazzling run past a number of would-be tacklers before firing home into the roof of the net to clinch all three points.
Despite the defeat, United are still12 points clear of City at the top of the table and have seven matches remaining to keep their distance with last season champions.
2012/13 Barclays Premier League season scores