Guly do Prado set Saints on their way with a well-taken brace and although Exeter had their moments, Southampton underlined their superiority with further goals from Adam Lallana and Lee Barnard.
Guly opened Saints' account with an emphatic finish midway through the first half after Lallana's attempted pass had deflected kindly into his path and the Brazilian, on loan from Italian club Cesena, took his league goals tally to four soon after with an easy finish.
Lallana stretched Southampton's lead even further when he worked a short corner with Richard Chaplow and his curling cross fooled Exeter keeper Paul Jones.
Substitute Barnard notched his sixth league goal of the season with a tidy finish after Ryan Dickson had knocked down Lallana's cross.
Exeter had their moments in the first half, particularly when Jamie Cureton made a mess of a volley when unmarked and Liam Sercombe's powerful shot was tipped over by Saints' keeper Kelvin Davis. But Exeter could have been on the end of a much heavier beating as Southampton wasted second-half opportunities to further improve their goal difference.