This was the first Manchester derby outside of England and it didn't disappoint the near capacity crowd in the NRG Stadium.
United boss Jose Mourinho claimed it was going to be like a training exercise - but he must have forgotten to tell his players.
The Red Devils were the brighter side and charged into a two-goal lead before half time thanks to impressive strikes from Romelu Lukaku and Marcus Rashford.
United made the best start and should have gone ahead in the opening minutes.
Lukaku skinned Fernandinho down the right flank before pulling the ball back to the unmarked Jesse Lingard.
But with the goal at his mercy, the England star miss controlled at the crucial moment and the chance was wasted.
Raheem Sterling tested David De Gea with a low strike before Kevin De Bruyne's delightful pass sent Phil Foden racing through but, like Lingard, the teenager blew his big opening.
Foden, from Stockport and a product of the City academy, looked sharp on his debut and showed no sign of nerves despite still being just 17.
United looked the most threatening though and came close again on 21 minutes when Antonio Valencia's clever pass set-up Henrikh Mkhitaryan.
The Armenian took aim before firing a powerful shot straight at Ederson, who parried the ball to safety.
Moments later Vincent Kompany blocked another effort from Lingard before Ander Herrera tried his luck from long range.
At the opposite end De Gea had to be at his acrobatic best to keep out a deflected shot from Sterling.
City should have had a penalty on 31 minutes when Patrick Roberts charged into the box only to be pulled back by Chris Smalling, but for some reason referee Ismail Elfath waved play on.
The decision proved costly when United broke the deadlock with two goals in 120 seconds before half time to leave Guardiola stunned.
Lukaku ended the stalemate on 37 minutes with a wonderful strike.
Paul Pogba's pass sent him clear behind the City defence and when Ederson charged out to avert the danger he got there too late.
Lukaku nudged the ball past him before curling the ball into an open goal from an incredibly tight angle.
Just 120 seconds later United scored again, Mkhitaryan sending in Rashford on the right who blazed his shot past a shell-shocked Ederson.
Guardiola replaced Sergio Aguero with Gabriel Jesus at the start of the second half and also threw on outcast Samir Nasri in the hope the duo could instigate a fightback.
But City came within a whisker of going 3-0 down when Rashford's speculative cross almost caught out Ederson by dropping into the far corner of the net.
It was turning into an uncomfortable night for the Brazilian goalkeeper, who watched Lukaku's blistering effort crash back off the woodwork moments later.
Pogba then lashed a drive into the side netting as United continued to dominate before seeing the game out to strike the first psychological blow ahead of the new Premier League season and leave Guardiola with much food for thought.
