Ryan Giggs and Robin van Persie gave Sir Alex Ferguson's men they victory they required and the Old Trafford club now only have themselves to blame if they are unable to maintain their runaway lead at the summit.
City have been in mediocre form of late, dropping points left, right and centre with draws against QPR and Liverpool and this heavy defeat at the hands of the Saints. It appears as though their title defence has already been relinquished.
Just behind them on the standings sits Chelsea who are within four points of second place courtesy of a 4-1 home triumph over Wigan Athletic thanks to goals from Ramires, Eden Hazard, Frank Lampard and Marko Marin.
The Blues are a point ahead of Tottenham in fourth following their 2-1 win over Newcastle United with Gareth Bale netting a double whilst their North London rivals, Arsenal, are clear in fifth after a 1-0 victory at Sunderland despite playing the final 30 minutes with ten men.
Elsewhere on the weekend, Norwich City and Fulham drew 0-0, Michu hit a brace as Swansea City cruised past a hapless QPR 4-1, Stoke City edged Reading 2-1 and Aston Villa moved out of the relegation zone with a 2-1 salute at home over West Ham United.
2012/13 Barclays Premier League season scores