Steven Gerrard scored two penalties and Luis Suarez was also on target as the Reds eased to their first victory at Old Trafford in five years.
The scoreline did not flatter Liverpool. It could have easily been five or six for Brendan Rodgers' side, who are now 14 points ahead of their old foes in the Barclays Premier League.
For a Croxteth-born man who started his career at Everton, losing to the Reds in a such a disastrous way was not easy for Rooney to take.
"It's one of the worst days I've ever had in football," the United striker told MUTV.
"It's hard to take. You have to give Liverpool credit - they played well - but it's difficult to take. Nobody wants to lose, especially in this way, in your own stadium. It's not nice."
Rafael handled the ball in the United box in the first half and Gerrard converted.
The Liverpool captain scored his second from the spot when Phil Jones clattered into the back of Joe Allen.
Gerrard could have had a hat-trick of spot-kicks when Nemanja Vidic was dismissed for a foul on Daniel Sturridge in the box, but he missed.
Still, there was time for Liverpool to find a third in the dying minutes as Suarez beat David de Gea from close range.
Rooney admits United were always going to struggle once they had gifted Liverpool their first goal.
"To go behind by one penalty was hard to take," Rooney said. "We had a game plan for the second half, which went out the window when they got the second penalty so early on.
"It made it an uphill battle to come back. I thought after that we had a couple of chances where I thought if we got one we could have gone for a second and maybe we could have done it.
"Obviously it didn't happen, though.
"Then, to concede a third penalty, even though they missed, was a big blow to us. We were then chasing the game with 10 men. That made it difficult for us and they kept the ball well to see the game out."
Vidic was unlucky to receive a second yellow as replays showed Daniel Sturridge appeared to dive, but Rooney had no complaints about any of the decisions.
"I haven't seen the penalties back again but from where I was standing on the pitch I don't think we can argue with them," the 28-year-old added.