Brad Boyes had the lone goal for Toronto (3-5-0), which lost its fifth-straight pre-season game.
Petr Mrazek made 28 saves as Detroit concluded the pre-season with a 6-0-2 record. Jonathan Bernier made 13 saves in the loss.
Athanasiou opened the scoring at 13:50 of the second period, using a burst of speed to split Morgan Rielly and Roman Polak before beating Bernier blocker side for his fourth of the pre-season.
Mantha gave the Red Wings a 2-0 lead with 54-seconds remaining in the second on a power play, beating a sprawling Bernier for his third of the exhibition schedule.