Two police tents have been erected outside shops and takeaways in the suburb, near the University of Manchester.
Manchester Evening News understands a young man has died after suffering stab wounds, but the cause of death is yet to be established.
A spokesman for Greater Manchester Police said: “At around 2am today, officers out on patrol were flagged down to an incident on Wilmslow Road in Manchester.
“Officers attended and established that one man had been seriously injured. They commenced CPR at the scene. An investigation is underway.”
The nature of injuries and the extent of them are yet to be confirmed by the force.
The crime scene is expected to be in place for the rest of the day.
Detective Superintendent Neil Jones, of Greater Manchester Police South Manchester Division, said: “I know that people in Manchester will be shocked and concerned by this incident. I share this concern and assure you that there is a dedicated team of specialist officers in the area who are investigating at pace to find the person responsible.
“Local officers will be patrolling the areas and I urge anyone with information or concerns to speak to those officers who are on hand to help and support you.
“Anyone with information should contact police via gmp.police.uk or 101 quoting 240 26/10/22. Information can be shared anonymously via the independent charity – Crimestoppers on 0800 555 111.”
Students at both University of Manchester and Manchester Metropolitan University live in the area.
Friends Becky and Alice, who study at Manchester Metropolitan University, said: “We’ve lived here for two years and nothing like this has ever happened before.”
Bus services are busy and have been diverted away from the route. People are being urged to avoid the area.
A tweet posted by Transport for Greater Manchester said: “A6010 Wilmslow Road, Fallowfield is closed between Moseley Road – Langley Road due to a police incident.
“Bus services are diverted and will use Dickenson Road – Birchfields Road – Moseley Road in both directions.”
Anyone with information should contact police via gmp.police.uk or 101 quoting 240 26/10/22. Information can be shared anonymously via the independent charity – Crimestoppers on 0800 555 111.