Benfica, who had won their previous eight Primeira Liga games, went ahead through Kostas Mitroglou only for Hector Herrera and Aboubakar to hand the visitors their first victory at the Stadium of Light for four years.
Porto, who completed a league double over their arch-rivals, are now within three points of Sporting and Benfica who are level at the top of the table.
Midfielder Renato Sanches, 18, the revelation of the season, set up the opening goal for the hosts with a delightful dinked pass to Mitroglou who beat Casillas with a scuffed shot.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
Herrera replied 10 minutes later when he was given too much space on the edge of the area and the Mexican midfielder drilled a low diagonal shot wide of Julio Cesar.
Casillas then sprang into action as he prevented Benfica taking a halftime lead by tipping a powerful Jonas drive over the bar.
The former Real Madrid goalkeeper again came to the rescue early in the second period when he brilliantly stopped Nicolas Gaitan who had a clear run on goal.
Aboubakar then burst past a defender and buried an angled shot past Julio Cesar in the 65th minute.
Casillas twice denied Benfica an equaliser, saving from Bruno Martins Indi after the Porto defender deflected a cross towards his own goal and making a point-blank stop with his feet from Mitroglou.
(Writing by Brian Homewood; Editing by Tony Jimenez)
