Their first home match of the season is against Paolo Di Canio's Sunderland team and August is rounded off with a trip to Norwich City.
Mauricio Pochettino's men will head to Liverpool and Manchester United in the opening 11 games of the campaign.
Promoted duo Crystal Palace and Hull City will also go to St Mary's during that period, before Southampton face a tricky run up to the turn of the year.
Back-to-back away games against Arsenal and Chelsea end November before Southampton entertain Manchester City and Tottenham Hotspur on the south coast in December.
They are away at last season's Championship winners Cardiff City on Boxing Day before going to Everton two days later, and then play host to Chelsea on New Year's Day.
The season concludes with a trip to Swansea City in their last away game before champions Manchester United visit St Mary's on the final day.