Police and paramedics were called to a house on Culcheth Lane, Newton Heath, at 00:45 BST on Sunday amid reports of an assault.
A woman, 38, was found with head injuries and she died shortly after.
The arrested man, 48, is in custody being questioned by Greater Manchester Police (GMP).
A post-mortem examination is due to take place later. The woman has not yet been identified.
A man has been arrested on suspicion of murder after a woman died from serious head injuries in Manchester.