Around 9.25pm last night (Sunday), officers received a report of a collision involving a vehicle and pedestrians in the Piccadilly Gardens area.
Officers attended and established that a double decker bus had collided with three pedestrians between stops C and D.
One pedestrian, a woman in her 50s, died.
Another woman in her 50s remains in hospital with serious injuries.
A man in his 60s received treatment for minor injuries.
The bus driver remained at the scene and assisted officers with their enquiries.
Investigators are particularly interested in hearing from anyone with dash or helmet cam footage of the collision or from Piccadilly in the minutes beforehand.
Anyone with information should contact the Serious Collision Investigation Unit on 0161 856 4741.
Information can also be shared anonymously via the independent charity - Crimestoppers - on 0800 555 111.
