Scores were locked at 20-all in the final minute on Wednesday when Blake Ferguson tiptoed the sideline, then found Tedesco for his second try of the night.
It came after Queensland forward Josh Papalii crossed in the 77th minute and debutant Ethan Lowe nailed a pressure conversion to level the game.
The dramatic finish ended a run of seven straight defeats in Origin deciders for the Blues, dating back to the start of the Maroons' dynasty in 2006.
It is also Mitchell Pearce's first series win over Queensland in eight attempts.