I live spitting distance from Main Street. Given its location, I had assumed that it used to be Main Street for East York, but it has always been part of Toronto. Yonge Street is the real main street of Toronto.
It was actually Main St. for the then independent municipality of East Toronto - annexed in 1908. East Toronto - Wikipedia.
There’s also a Main Street on New York’s Roosevelt Island. (One of the first Google results is an article about how no one likes it, though I gather it’s changed for the better since Cornell built a tech campus on the island’s south end.)