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.

Southwark Crown Court was told that Mr Clifford exposed himself to the woman, who cannot be named for legal reasons.
She claims Mr Clifford forced her to perform a sex act on him and that she thought he would "rape or kill" her.
Mr Clifford denies indecent assault in his London office in the 1980s. The prosecution has finished its case and the trial was adjourned until Monday.
The court heard that Mr Clifford was asked about the allegation in his police interview.
Det Sgt Jason Price, giving evidence, asked whether Mr Clifford remembered coming out of his office, blocking the alleged victim's access to a stairwell and exposing his penis.
Mr Clifford said: "No comment."
Det Sgt Price then said in the interview: "You gyrated around, so one would assume by that it means moving your hips around."
Mr Clifford replied: "What? Dancing or something? No comment."
The alleged victim claimed that he put her hand on his penis and she said "I don't want to" but she "did as she was told" and only stopped when they were disturbed by a knock on the door.
At the start of the interview, Clifford gave a statement in which he denied the allegation.
His statement said he had never engaged in sexual relations with someone without their consent and "neither have I ever needed to coerce someone".
After his statement was read out in the interview, he answered "no comment" to the majority of the questions and said of the allegation: "Everything about it is totally untrue."
Some of the biggest names in show business, including pop mogul Simon Cowell, late reality TV star Jade Goody and boxer Muhammad Ali, were represented by Mr Clifford, of Hersham, Surrey, during his career
Mr Clifford will give evidence on Monday.
Motorists in Manchester are being frustrated by the appearance of yet another hole in a city-centre road.
[NEXT_CONCEPT]
Former celebrity publicist Max Clifford "gyrated" in front of a 17-year-old girl, a court has heard.