A frantic start to the game saw four goals in 24 minutes and that was all the time needed for De Bruyne to earn his hat-trick.
The midfielder showed his class just seven minutes into the game when he calmly slotted home into the bottom corner.
A wonderful Wolves counter-attack then gave the hosts hope as Leander Dendoncker was on hand to finish off the move from 10 yards.
Just when the hosts had their tails up City and De Bruyne struck again. A Jose Sa mistake handed it to the midfielder from 20 yards and his deflected effort crashed into the roof of the net.
That was just the beginning, however, as he added his third after 24 minutes with an excellent sweeping finish all of his own making from outside the box.
Wolves came out in the second half and had some momentum going forward but struggled for the final ball, before De Bruyne added the nail in the coffin.
His positioning was bang on as he popped up from 10 yards to collect a loose ball and tuck the ball home, before Raheem Sterling added a late fifth.
Bruno Lage, albeit absent from Molineux with Covid-19, made one change to his side but stuck with the 3-5-2 formation.
Romain Saiss missed out on the squad through injury, meaning Willy Boly moved to the left of the back three and Jonny Castro Otto slotted into the right side. As a result, Chiquinho was handed his first Wolves start and came in at right-wing-back.
Saiss’ omission meant Yerson Mosquera came into the side and made the bench.
Pep Guardiola made three changes to his City side as they started in a 4-3-3 formation.
Fernandinho started in his unnatural position of centre-back, while Bernardo Silva and Phil Foden also came in.
Within two minutes, City had a huge chance. De Bruyne flashed the ball across goal and Foden was inches away from connecting with it as he slid in.
But all it took was seven minutes for the visitors to take the lead. A delightful pass from Silva slipped De Bruyne through and the midfielder slotted home into the bottom corner.
Shortly after the re-start Chiquinho had the home fans off their seat when he raced down the right flank and towards goal, but a last-ditch sliding tackle from Aymeric Laporte denied him a shooting opportunity.
Just four minutes after City’s goal, Wolves levelled through a superb counter-attack. Raul Jimenez raced into the City half and fed Pedro Neto, who picked out a perfect pass for the oncoming Dendoncker to finish from 10 yards.
In what was a frantic start to the game, it only took another four minutes for another goal as City regained the lead. De Bruyne played in Sterling who went to attack the ball before pulling out, meaning goalkeeper Sa blocked the ball rather than collecting it, as he anticipated Sterling’s touch. De Bruyne then picked up the loose ball to notch his second of the game.
Wolves were struggling to get on the ball as City dominated possession and after 24 minutes De Bruyne sealed his hat-trick. In a moment of pure quality from the midfielder, he picked the ball up on the right, cut across goal and smashed the ball into the bottom left corner with his left foot.
One Wolves attack saw Rayan Ait-Nouri release Chiquinho, who took on Oleksandr Zinchenko down the right flank. Wolves were calling for a penalty as Zinchenko slid in, but replays showed he won the ball.
After the fast goalscoring start, the game hit a lull leading into half-time. City largely dominated possession and saw out the rest of the half fairly comfortably, leaving Wolves with plenty to do.
In the opening minutes of the second half Sterling netted but was then adjudged to be offside. The winger was marginally offside in a very tight call.
Wolves were managing to fashion some chances and break away from the City defence, which in turn got supporters off their feet, but after an hour they were still searching for the one goal that would get them back into the game.
Those hopes were dashed moments later when De Bruyne added his fourth of the game. A sweeping City move saw the midfielder feed Foden, whose cut back was defended by Ait-Nouri, but the fall fell to De Bruyne for an easy finish from 10 yards.
Wolves raced up the other end and were demanding a penalty when Neto cut inside Fernandinho and was brought down as he turned inside, but the Brazilian got a knee to the ball and the spot kick was not awarded.
City were still slick and dangerous going forward and De Bruyne almost added an assist when his pass resulted in Foden hitting the post.
Sterling added a late fifth for City with a simple back post finish as Wolves fell to a heavy 5-1 defeat.
Wolves: Sa, Jonny, Coady, Boly, Chiquinho, Dendoncker, Neves, Moutinho (Cundle, 85), Ait-Nouri, Neto (Trincao, 72), Jimenez (Hwang, 72).
Subs: Ruddy, Mosquera, Gomes, Hoever, Marcal, Silva.
Man City: Ederson, Cancelo, Fernandinho (Mahrez, 77), Laporte (Ake, 61), Zinchenko, Rodri, Gundogan, Silva, De Bruyne, Sterling, Foden (Grealish, 81).
Subs: Steffen, Egan-Riley, Mbete, Lavia, Palmer, Jesus.