Waitrose opened its 3,337 sq ft convenience store in Manchester House on Bridge Street in Spinningfields on Thursday.
The food retailer agreed a lease on the property with Allied London in September for an undisclosed sum.
Spinningfields Management Company said the new store has made a welcome addition to the area which includes IM Properties' retail and office development The Avenue nearby.
Spinningfields comprises 4.6m sq ft of mixed use development between the River Irwell and Deansgate in Manchester.
Waitrose currently has stores in Altrincham, Cheadle Hulme, Wilmslow, Sandbach and is opening another convenience store in Knutsford in spring next year.