Stewart Downing fired home a 16th-minute penalty after City captain Richard Dunne was harshly sent off for bringing down Tuncay Sanli and eight minutes before the break Afonso Alves slotted home the second.
After the break it was one-way traffic but the extent of City's capitulation would be concerning for whoever is in charge at the start of next season.
Fabio Rochemback curled in a 30-yard free-kick and Jeremie Aliadiere fired home with Elano getting a consolation before Alves completed his hat-trick in the final minute.
City boss Sven Goran Eriksson could offer no explanation for the result other than bad luck.
"You can use whatever word you want and I would probably agree," he said. "It started badly when Benjani was injured after just a couple of minutes.
"A little bit later penalty and a red card for our captain. I don't think he (Dunne) tried to foul him. I think they crossed but it is difficult to be the ref in this case.
"It was a collision and it was the wrong place. I don't think the ball has gone to the striker, it has gone straight to Isaksson but I think the referee maybe must send him off in a place like that."
The victory was Boro's biggest in the top flight since they put eight past Huddersfield in 1950.
Manager Gareth Southgate was in understandably upbeat mood afterwards and opened his press conference by cracking a joke.
"There is no point in me saying too much because you're only going to put about Sven tomorrow," he said. "It was a mad day wasn't it? I think from our point of view, I don't think we've had a lot of good fortune this year and we seemed to get all our good fortune and all our goals in one day.
"Certainly, the turning point was the sending off and the important goal for us was the third because, even at 2-0, they have got some good players who could still keep the ball well.
"But we scored some brilliant goals and played some really good football and it was nice for our players to play without pressure. That is the first time we have been able to do that this season."