Goals from James Chester and David Meyler had the Tigers two up inside 13 minutes at the KC Stadium but United pulled one back through Chris Smalling before Rooney's brilliant volley from 25 yards made it 2-2.
Hull were unlucky not to restore their lead after the break when Alex Bruce saw his header come back off the bar, and within moments United profited to the full when Chester put through his own net under pressure from Rooney.
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."