The crash happened just after 3 a.m. on Bloor Street West between High Park and Clendenan avenues.
The driver, identified by Toronto paramedics as a man in his 50s, has serious but non-life-threatening injuries.
Bloor Street West was temporarily closed in both directions as the Toronto Police Traffic Services Unit investigated, but has since reopened.
Anyone with information should contact police at 416-808-1900 or Crime Stoppers anonymously at 416-808-8477 (TIPS) or www.222tips.com.