Armed officers were sent to the Hilton on Deansgate in the city centre after police were flagged down by the victim shortly after 11.10am on Monday, Greater Manchester Police said.
Three men and two women were arrested, said a GMP spokesman, who added: "This is not thought to be terrorism related nor thought to be a random attack."
Anthony Hilton, who works in a nearby letting agents, said the victim had been taken away in an ambulance.
"One of our colleagues walked past and saw a lady on the floor with what appeared to be her throat slit," said Mr Hilton, 32, from Manchester.
He described the woman as well dressed and in her thirties but could not comment on her condition as she was taken away.
"There must have been 15 undercover and normal police cars out in the street.
"Police were running to and fro from the car park and the Hilton Hotel," he added.
Police said the victim was being treated for lacerations to her neck.
Witnesses said on social media the victim ran screaming into street and that the three men were arrested shortly afterwards.
Two women were later seen being led from the hotel in handcuffs, one in silky pink pyjamas, according to one Twitter user.
Police said crime scenes had been set up in one of the hotel rooms and outside the hotel itself.
Officers could be seen speaking to other guests and hotel staff in one of the bars of the Hilton, which occupies part of the 47-floor Beetham Tower, which is described by its developers as the tallest residential buildings in Europe and the seventh tallest building in England.