After a brief instant-replay review, the play was confirmed, giving Lawrie a two-base hit against Tribe reliever Scott Atchison. The next batter, Blue Jays catcher Erik Kratz, grounded out to end the inning.
Francona has challenged nine plays this season and only three have been overturned.
With the Indians trailing 4-1 in the fifth inning, Lawrie split the left-center field gap with a double. Toronto's second baseman hustled around first base, but did not step on top of the bag as he ran for second. Replays showed dirt flying into the air near first and it was detemined that the front of Lawrie's right foot made contact with the base.
Toronto manager John Gibbons used a challenge in the bottom of the eighth inning with the Blue Jays losing, 4-2.
With two out and Melky Cabrera at the plate, Jose Reyes attempted to steal second base.
Indians catcher Yan Gomes made the throw to second, with shortstop Asdrubal Cabrera covering the base. Cabrera applied the tag to Reyes, who slid in head first. He was called out, and after a review of 1:36, the ruling was confirmed.