The closure is due to the expiration of the shop's lease, reports GamesIndustry International, and does not mark the beginning of a new wave of closures.
"We can confirm that we will be closing our Oxford Street store on September 8, 2012 due to the expiration of the lease," reads a statement from GAME.
"Our West End customers can visit our concession in Hamleys on Regent Street, our flagship store in Westfield Stratford, or our websites at http://www.game.co.uk or http://www.gamestation.co.uk. We also have stores in Hammersmith, Surrey Quays, and Westfield White City.
"We're actively looking at other retail options in the West End, and the Oxford Street team have been temporarily relocated to other stores across London and the South East."
Rumours of the Oxford Street store's closure began to surface in May, following reports that the company owed three months worth of rent.
The dispute between administrators PriceWaterhouseCoopers (PwC) and landlord Lazari GP, which was tied into GAME's descent into administration, appeared to have been settled following OpCapita's takeover.
A total of 277 shops and 2,000 jobs were lost as a result of the GAME Group's struggles. The remaining 333 stores have largely remained untouched.
GAME Group's entry into administration reportedly drove yearly video game sales down by 34%.