Cano had two RBI singles during New York's 12-run first inning, the most runs scored in an opening inning by the Yankees and the most in any inning for them since 2005.
New York sent 15 men to the plate in the 70-pitch, 40-minute first, banging out 10 of their 24 hits and chasing Orioles starter Zach Britton (6-8) after recording just one out among the first 10 batters.
Britton was charged with nine runs (six earned) on seven hits, walking one while throwing 43 pitches.
Nick Swisher contributed three hits, including a two-run homer, Mark Teixeira went 3-for-5 with a two-run double and Andruw Jones contributed a solo home run for the Yankees, who recorded an 8-3 victory in the day's first game.
Ivan Nova (9-4) earned the win with two runs on six hits over seven innings, walking one and fanning six.
Vladimir Guerrero went 4-for-4 with a two-run home run for Baltimore.