Despite the absence for City of goalkeeper Joe Hart and captain Vincent Kompany, it was Southampton who struggled to settle early on.
The Saints were found wanting at the back during the early stages, with Maarten Stekelenburg being called into a series of nervy saves and his defence failing to keep the waves of City offensives at bay.
The home side opened the scoring on nine minutes when the impressive Raheem Sterling dispossessed the unconvincing Maya Yoshida—admittedly playing out of position at right-back—and crossed for De Bruyne to finish from close range.
Delph, making his first start as a replacement for Fernando, made it 2-0 11 minutes later when his long-range strike took a deflection and trickled past Stekelenburg.
While Virgil Van Dijk went close to halving the deficit with an effort which struck the crossbar, City held on to take a 2-0 lead in at the break.