City sink Saints to maintain title charge
Victory saw City close to within a point of Liverpool with a game in hand and leapfrog Chelsea into second place.
But Chelsea, who've also played one game more than City, will go a point clear at the top if they beat Stoke at Stamford Bridge in Saturday's late kick-off.
Liverpool are away to West Ham on Sunday.
Everton and Arsenal, fifth and fourth respectively before the weekend, clash at Goodison Park on Sunday.
The opening four goals at Eastlands all came in the first half with City's Yaya Toure and Saints' Rickie Lambert both scoring from the penalty spot before Samir Nasri and Edin Dzeko scored in stoppage-time to make it 3-1 to Manuel Pellegrini's men.
However, controversy surrounded the goal from Nasri that made it 2-1 with David Silva, who played in the French midfielder, offside when he received the ball only for referee Chris Foy and his linesmen to let play continue.
City substitute Stevan Jovetic completed the scoring nine minutes from time.
"I haven't seen it (City's second goal) yet but it is the referee who decides," City manager Manuel Pellegrini told Sky Sports.
"I don't think the difference between the two sides was just one goal," the Chilean added.
Defeat was made worse for Southampton by a first-half injury suffered by Jay Rodriguez, one of their England strikers, that placed a huge question mark against his chances of making into Roy Hodgson's squad for this June's World Cup finals in Brazil.
- 'Linesman killed the game' -
Rodriguez landed badly after jumping to control the ball in the 26th minute and clutched his knee in agony before being carried off on a stretcher.
"I don't know how Jay Rodriguez is. It's not looking good but we'll be assessing it in Southampton," said Saints boss Mauricio Pochettino, who was furious at the decision to let Nasri's goal stand.
"This action from the linesman for the second goal killed the game, the linesman killed the game," he added.
Meanwhile Juan Mata scored twice as Manchester United moved above Tottenham, who face relegation-threatened Sunderland on Monday, and into sixth place with a 4-0 win away to Newcastle.
Fresh from their morale-boosting 1-1 Champions League draw against title-holders Bayern Munich at Old Trafford on Tuesday, David Moyes's side took the lead at St James' Park courtesy of Mata's superb 39th minute free-kick that curled into the top corner.
And the Spain midfielder doubled United's lead five minutes after half-time when, after good work by Japan's Shinji Kagawa and Mexico's Javier Hernandez, he slotted home from close range.
Hernandez then made it 3-0 in the 65th minute after being played in by Kagawa and substitute Adnan Januzaj completed the scoring in the final minute of normal time.
Fulham moved off the bottom of the table with a 2-1 win away to Aston Villa.
The Cottagers remained in the relegation zone but were now just five points shy of safety with five games left.
Fulham took the lead courtesy of Kieran Richardson's 22-yard shot in the 61st minute at Villa Park.
But Birmingham side Villa equalised nine minutes later though striker Grant Holt's header.
However, the west London side had the final say four minutes from time through Hugo Rodallega's glancing header from Lewis Holtby's cross.
Jason Puncheon scored two goals as Crystal Palace moved seven points clear of the relegation zone with a 3-0 win Cardiff that left the Welsh club in the bottom three.
The winger opened the scoring in the 31st minute before Joe Ledley doubled the lead against his old club in the 71st minute.
Puncheon put the result beyond doubt with a brilliant curling shot from 25 yards two minutes from time.
West Bromwich Albion went five points clear of the drop with a 1-0 victory away to Norwich thanks to Morgan Amalfitano's stunning 40-yard strike in the 16th minute at Carrow Road.
And Hull beat mid-table rivals Swansea by the same scoreline thanks to George Boyd's 39th minute-goal at the KC Stadium.