The victim, named locally as Sait Mboob, was stabbed at about 20:40 BST on Tuesday during a reported fight on Crosshill Road.
Three others, two 17-year-old boys and a man, 18, are being treated in hospital for serious injuries after also being stabbed.
The arrested teenager is being questioned in police custody.
Detectives earlier searched three properties in Ardwick as part of the investigation, Greater Manchester Police said.
Formal identification and a post-mortem examination are yet to take place.
Supt Dave Pester asked people in the community to come forward with information, adding: "I urge you to tell us what you know. A family has lost their son and we need your help to stop this from happening again."
Police will remain in the Moss Side area, he added.
A 17-year-old boy has been arrested on suspicion of murder after an 18-year-old was stabbed to death in Manchester.