The collision, which resulted in a fire, happened shortly after 12:30 am.  on Guildwood Parkway between Galloway Road and Navarre Crescent.
Toronto medics said a male victim suffered burns and is in serious but stable condition.
Another man and a woman were taken to a local trauma center as a precaution, they said.
Police are advising motorists to consider alternate routes and avoid the area if possible, as Guildwood Parkway is closed from Forsythia Drive to Navarre Crescent is closed as the Traffic Services unit investigates.
Anyone with information about this collision should contact Toronto Police at 416-808-2222 or 416-808-1900 or Crime Stoppers anonymously at 416-222-8477 (TIPS) or www.222tips.com.