Jesus Navas put City in front after just 13 seconds and things went from bad to worse for a lacklustre Tottenham side as ruthless City ran riot at the Etihad Stadium.
Sandro scored an own goal before the prolific Sergio Aguero helped himself to a brace. His striker partner Alvaro Negredo got in on the act with a stunning goal of his own and Navas completed the rout with his second goal right at the death.
Big things were expected of Spurs at the start of the season, but this was their fourth defeat in the Premier League and they are now down in ninth place.
Villas-Boas was baffled by such a heavy defeat that he did not see coming.
"(It was a) difficult start, conceding after (almost) 15 seconds puts your plans in doubt, it's difficult to take," he said. "I think we had a very good reaction to the (opening) goal, that’s probably the only positive of the game we have.
"Everything went bad for us, from being one of the best defences in the country to suffering six goals, there's not a lot I can say.
"City were excellent, we were extremely poor today, and we paid a big price. From the moment we suffered the fourth goal we mentally weren’t playing the game."
