The Belgian put the game to bed with a hat-trick in a devastating 18-minute spell in the first half, before notching a fourth after the break as the away fans alternated between chanting "Kevin De Bruyne" and "Champions of England".
The win leaves Pep Guardiola's side top on 89 points, three ahead of Liverpool whom they also lead on goal difference, with the title now firmly in their sights.
A second consecutive Premier League title would assuage disappointment at their Champions League exit, after City fell in the semis and Liverpool reached the final.
Wolves had briefly threatened an upset, when Leander Dendoncker made it 1-1 after a great break, before the De Bruyne show rolled on. He scored a fourth from close range in the 60th minute, before team mate Raheem Sterling completed another easy win for City with his 84th-minute goal.
Wolves stayed in eighth position on 50 points.