The victory was Saints' sixth top-flight win and their best ever start to a top-flight season, trumping the 1983-84 campaign when they finished runners-up.
Earlier this week, England boss Hodgson called up Saints trio Jay Rodriguez, Rickie Lambert and Adam Lallana for the upcoming friendlies with Chile and Germany.
Mauricio Pochettino, winner of October's manager of the month, named six English players in the starting line-up on the south coast, although it was impressive French midfielder Morgan Schneiderlin who headed home the opener.
Lambert provided the assist and was soon on the scoresheet himself, continuing his 100 per cent record from the spot for Saints by rifling past Steve Harper.
Lallana earned the penalty and then went on to score one of the best solo goals seen at St Mary's, jinking his way through the City defence and striking low past Harper.
Steve Bruce's side improved after the break and pulled one back through Yannick Sagbo, but Saints held firm and grabbed another through substitute Steven Davis to extend their unbeaten league run to seven matches.
In truth, City were lucky not to be further behind at half-time after a miserable first half which began with a Lallana cross that just evaded Lambert.
Tom Huddlestone did well to stop a Rodriguez cutback finding James Ward-Prowse soon after, before Southampton found the opener in the 16th minute.
Nathaniel Clyne, a player Hodgson revealed is close to a call-up, sent in an excellent cross to the back post, where Lambert knocked back under pressure for Schneiderlin to head home.
Saints were being allowed to boss the play and it was no surprise when City went further behind on the half-hour mark.
Meeting a Lambert through ball, Lallana was sliced down by onrushing Harper in the penalty box and talisman Lambert smashed home the spot-kick.
Saints fans interchanged the names of Lambert, Rodriguez and Lallana as they sung "he's off to Brazil" - chants that grew for the latter after a stupendous solo effort.
Picking up the ball midway through the opponents' half, Lallana drifted to the left, rode the challenge of Curtis Davies and ghosted past Ahmed Elmohamady, before slotting home right-footed past Harper from an acute angle.
It was an exquisite goal and one City should have done better to stop. Maynor Figueroa attempted to pull one back in first half stoppage time, only to see his header cleared off the line.
Robert Koren replaced Elmohamady as Bruce went to four at the back for a second half in which they were much improved.
Perhaps overconfident, Saints looked to let their foot off the gas and Victor Wanyama was caught out 10 minutes after the restart.
Collecting a simple Artur Boruc pass, the Kenyan was dispossessed and Sagbo struck home from the edge of the box - the first goal conceded by Saints on home turf in over 10 hours of football.
David Meyler cleared a Schneiderlin effort off the line from a corner, with substitute Dani Osvaldo getting a header on goal as the match entered the closing stages.
Substitute Davis added extra gloss to the win with two minutes remaining, thrashing home another after collecting yet another impressive Clyne cross.