Pep Guardiola’s side – aiming to reclaim the title they lost to Liverpool last term – were featuring for the first time in 2020-21 due to their involvement in the previous campaign’s Champions League knockout stage.
But City made up for lost time in a dominant first 45 minutes on Monday as De Bruyne capitalised on a rash challenge to break the deadlock from the penalty spot, before Phil Foden added a stylish second.
Wolves, who did the double over City last season, enjoyed a better spell after the break and belatedly netted through Raul Jimenez.
Yet De Bruyne’s tackle in the final seconds allowed Gabriel Jesus to strike a deflected clincher.
In control from the outset, City were gifted the opener as Romain Saiss lunged in on De Bruyne just inside the right edge of the area, prompting a spot-kick the reigning PFA Players’ Player of the Year tucked away.
The visitors remained on the front foot and had their second 13 minutes before the break as De Bruyne fed Raheem Sterling, who cut a pass back for Foden to slide into the net.
Wolves came from two down to win the corresponding fixture last season, but De Bruyne could have put the result beyond doubt heading into half-time had the advancing Rui Patricio not blocked well.
There was improvement from Wolves following the restart, though, and Daniel Podence came to the fore, blasting past the top-left corner.
Surprisingly dummying for Ruben Neves to scuff a shot goalwards and then lifting a lob over Ederson’s crossbar.
Jimenez was uncharacteristically wasteful as he turned a low finish wide and his goal 12 minutes from time – courtesy of a powerful header from Podence’s cross – could not inspire an improbable rescue act.
Instead, De Bruyne pinched possession and Conor Coady’s touch carried Jesus’ shot past Patricio to seal the points.
Wolves: Rui Patricio, Traore, Boly, Coady, Saiss, Marcal (Ruben Vinagre 8), Joao Moutinho (Dendoncker 78), Neves, Pedro Neto (Silva 78), Jimenez, Daniel Podence
Subs not used: Vitinha, Ruddy, Kilman, Rasmussen
Goals: Jimenez 78
Manchester City: Ederson, Walker, Stones, Ake, Mendy, Fernandinho, Rodri, Foden, De Bruyne, Sterling (Torres 82), Gabriel Jesus
Subs not used: Steffen, Mahrez, Otamendi, Delap, Doyle, Bernbe
Booked: Mendy, Gabriel Jesus, Rodri
Goals: De Bruyne 20 pen, Foden 32, Gabriel Jesus 90
Ref: Andre Marriner (West Midlands)