First-half goals from Richard Chaplow and Jos Hooiveld enabled Southampton to move five points clear at the top of the Championship.
Chaplow opened the scoring when he fired low past Paul Jones and it was 2-0 three minutes later when Hooiveld netted from close range.
Peterborough's Lee Frecklington was sent off before the break for a second yellow card.
Emile Sinclair pulled one back for the visitors late on.
The home side should have been out of sight before Sinclair raced onto a through-ball to beat Kelvin Davis in the 76th minute, but Jones saved well from Rickie Lambert on three separate occasions.
Southampton's Steve De Ridder also missed a good chance just before the end to make sure of the points as he fired wide.
The win was a 17th straight home league victory for Nigel Adkins' side, who have made their best start to a season in 55 years.
They extended their lead at the top of the table as West Ham were held to a goalless draw at home by Bristol City.