The Norwegian marksman scored twice alongside efforts from Jack Grealish and Julian Alvarez in a classy performance from Pep Guardiola's side, while Sekou Mara struck a consolation for a Saints outfit who had nothing to show for their fleeting threats in the first half.
Despite the 18-place and 41-point chasm separating the two sides in the Premier League table, Southampton were not afraid to ask a few questions of the Man City backline early doors, even though the champions dominated possession as expected.
With 15 minutes gone, a short corner from Man City failed to reach Kevin De Bruyne thanks to an alert Kamaldeen Sulemana, who intercepted the set-piece and raced away down the other end, but Nathan Ake and Ederson did enough to put the former Rennes man off as a heavy touch saw the chance go begging.
Carlos Alcaraz headed wide in the 20th minute as the St Mary's faithful just started to believe that little bit more, and the home crowd could afford themselves a chuckle in the 41st minute as Haaland headed wide from close range, but the travelling fans at the opposite end of the field thought that the Norwegian's effort had gone in.
However, smiles on Saints fans' faces were soon wiped out just before the break, as Haaland made no mistake with a second header from De Bruyne's 100th Premier League assist to break the deadlock.
De Bruyne joined Ryan Giggs (162), Cesc Fabregas (111), Wayne Rooney (103) and Frank Lampard (102) as just the fifth player to set up a century of Premier League goals - doing so in a record 237 games - as Guardiola's men entered the break with a slender lead despite Southampton's praiseworthy efforts.
The Saints' uphill battle would become even steeper in the 58th minute, as De Bruyne released Grealish down the left during a quick break, and the in-form Englishman's low effort was kept out by Gavin Bazunu before he pounced on the rebound to double the champions' advantage.
From goalscorer to provider in the blink of an eye, Grealish stood and watched the mastery of Haaland after chipping a ball to the 22-year-old at the back post in the 68th minute, as he completed his brace with a sublime acrobatic kick to bring up 30 Premier League goals.
Any hopes of a miraculous Southampton comeback had ostensibly been wiped out, but the Saints offered their fans a minor slice of hope in the 72nd minute, as Moussa Djenepo weaved his way in and out of challenges before laying off fellow substitute Mara to side-foot home into the corner.
However, it took just two minutes for the Citizens to restore their three-goal cushion, as Kyle Walker-Peters scythed down De Bruyne in the area, and Alvarez did the rest from 12 yards - crashing his penalty down the middle of the goal.
Man City now prepare to tackle Bayern Munich in Tuesday's Champions League quarter-final first leg, by which point Arsenal could have restored their eight-point lead in the Premier League with victory over Liverpool on Sunday afternoon.
Meanwhile, Southampton remain in 20th place with 23 points - four adrift of safety with eight games left to play - and Selles's men are back in action at St Mary's against Crystal Palace next Saturday.