The PR agency has taken 7,000 sq ft at 196 Deansgae on a ten-year lease with a five-year break.
The six-storey grade-2 listed building is one of the locations linked to Project Tomorrow, which is expected to bring around 20 global technology companies to the city as part of an investment in the region's digital economy.
Citypress will relocate in March from its current offices at Bank House, Faulkner Street.
The agency employs 50 people with fee income of more than £3m.
Edwards & Co represented landlord Commercial Estates Group. Citypress were unrepresented.
Charles Tattersall, managing director of Citypress, said: "Manchester has been the home of the business for over 50 years and we're proud to be making a commitment to continue expanding here. With Media City, The Sharp Project and Project Tomorrow, it's an ideal location for a growing media business like ours, providing the infrastructure, reputation and access to talent that we need."
The business recently expanded its senior team in Manchester, appointing a trio of new account directors including Victoria Blakeley from Weber Shandwick, Liz Larvin from the British Chambers of Commerce in London and Mark Lester from The Royal Bank of Scotland Group.