There were no reports of injuries.
Traffic was rerouted throughout the afternoon rush hour while police investigated.
Construction workers told CBC News one pane of glass was being changed when it fell. That pane hit a window, dislodging another pane of glass. Both then hit the ground on Bay Street.
The accident happened at about 4 p.m and police say the intersection will remain closed until at least 9 p.m. while crews clean up.
This is the second time glass has fallen from the Trump Tower.
The last time was in March.
In a statement released Wednesday evening Trump Tower said in a statement "this incident is not related to the structure of the building" and that "management is working with Toronto Police on the scene to investigate the cause."