Goals from James Chester and David Meyler had the Tigers 2-0 up inside 13 minutes but United quickly pulled one back through Chris Smalling.
Rooney hit a brilliant volley to net his 150th Premier League goal and draw the Red Devils level, and Chester's own goal in the second half completed the turnaround.
The win continues United's recent resurgence under David Moyes, and their resilience in coming from behind against a well-drilled Hull outfit was of particular satisfaction to Rooney.
"We didn't start well enough today. Two-nil down we had to dig deep and show our fighting spirit. We've done that and this is a massive result for us," Rooney told Sky Sports 1.
Asked about United's slow start to the match, Rooney said: "It was just poor defending. It was my fault for the first, I've let James Chester go, and then a sloppy goal.
"We had to come back and try and get an early goal after they scored the two."
Rooney's milestone strike after 26 minutes was straight out of the top drawer, and the forward added: "The ball's bounced nicely for me and I've had a go.
"It was a good goal for us at a good time of the game."