It happened at the intersection of Edinburgh and Willow roads at around 11:30 a.m.
Police said the man was crossing the intersection when he was struck by a car being driven by a 50-year-old Guelph woman.
The car then partially went up a cement retaining wall.
The man in the wheelchair was taken to hospital, while the driver was not hurt.
The intersection was closed for several hours through the afternoon for the investigation.
Police said they have already received information from witnesses who stayed at the scene but are still asking for those who saw the collision to come forward.
Investigators with the traffic unit can be reached at 519-824-1212 ext. 7514.
Police didn’t comment on any pending charges but said the investigation is ongoing.
With the provincewide Road Safety Week upon us, Guelph police are also reminding drivers, cyclists and pedestrians to stay alert, avoid distraction and slow down.