Pep Guardiola's side spent much of the night banging their heads against the red and white brick wall assembled by Atletico's massed defence at the Etihad Stadium.
But Guardiola sent on Phil Foden midway through the second half and his sublime pass teed up De Bruyne to finally reward City for their territorial dominance.
While Guardiola launched a water bottle in a frenzied celebration that underlined what a testing night it had been for his team, the City boss will know the tie is far from over.
At the start of a season-defining 11 days for treble-chasing City, this was a qualified success that justified their patient performance.
But Atletico have already knocked out Manchester United in the last 16 this season, while Liverpool fell victim to Diego Simeone's side when the Reds were the holders in 2019-20.
The Spanish champions will still believe they can cause another surprise in the second leg in Madrid on April 13.
City have no margin for error over the next two weeks as the Premier League leaders host Liverpool, just a point behind them in the title race, on Sunday.
They head to Madrid next week before facing Liverpool again in the FA Cup semi-finals at Wembley three days later.
Guardiola has often been criticised for his curious team selections in previous Champions League knockout stages defeats with City.
That charge elicited a scathing response from Guardiola on Monday when he joked he always "over-thinks" his "stupid" tactics.
However, Guardiola's game-changing decision to introduce Foden should silence a few of his critics after it turned a difficult evening into a vital victory.