A 5ft x 3ft (1.5m x 1m) void appeared on Whitworth Street on Sunday, resulting in the road's closure between Princess Street and Oxford Street.
A section of the busy Mancunian Way has been closed since August, after two holes opened up. Replacement sewer pipes are being installed.
United Utilities said sewers underneath Whitworth Street have not been damaged.
"Non-urgent" roadworks in other parts of the city have been suspended until after Christmas in order to relieve congestion caused by Mancunian Way's partial closure.
Councillor Pat Karney, city centre lead for Manchester City Council, said Whitworth Street should be repaired in time for Monday's evening rush hour.
He described the appearance of the latest hole as "incredibly unfortunate".
"The council has placed a moratorium on all non-urgent roadworks, but this is the last thing we needed at the moment," he added.
He said the council will investigate why the city is being "blighted" by holes.
A 40ft (12m) wide sinkhole opened up in August on the Mancunian Way after heavy rainfall, while another hole appeared a month later.
Motorists in Manchester are being frustrated by the appearance of yet another hole in a city-centre road.