The Hammers had been due to host the Saints on Saturday August 19, but will now travel to St Mary’s - six days after the athletics finishes in east London.
READ MORE: Premier League week-by-week fixtures guide
West Ham will now host Southampton at the London Stadium on Saturday March 31.
An agreement between the two clubs and the Premier League means West Ham will now play their first three top flight games away from home.
The London Stadium’s first match of the campaign will be on September 9 against Huddersfield.
Putting the London Stadium back into ‘football mode’, which includes re-erecting temporary seating over the athletics track, takes several weeks. The club are obliged to leave a ‘clean stadium’ for both the World Para Athletics Championships (July 14-23) and World Athletics Championships (August 4-13).
The club store and ticket office will remain open throughout the summer but West Ham branding has already been removed from the outside of the stadium.