The estate agency has taken a lease on the vacant Mayfair Court office in Wilmslow Road for its first Fallowfield branch.
Work will now begin on preparing the 2,000 sq ft branch for the team to occupy, with an open date set for the middle of November.
The expansion into Fallowfield is part of homes4u's plan to strengthen its position in the student lettings sector, and continue to expand its sales division.
Other homes4u branches are in Withington, Manchester city centre and Altrincham.
The landlord at Mayfair Court is Greystar.