The Raptors came into the final quarter trailing by nine points but went on a 10-0 to run grab the lead.
Lowry's 3-pointer with 3:15 remaining put Toronto ahead 98-93 and the Raptors went on to log the first victory by an opponent in Oklahoma City this season after the Thunder had begun 13-0 at home.
Amir Johnson had 17 points with 13 rebounds and DeMar DeRozan scored 17 for Toronto, which recorded a fourth straight road win for the first time since 2002.
John Salmons scored 14 points off the bench.
Russell Westbrook had 27 points, nine rebounds and five assists for Oklahoma City, which had its nine-game overall winning streak snapped.
Kevin Durant added 24 points and eight rebounds but committed a game-high six turnovers.