With their revamped bullpen allowing only one runner in three innings, the last-place Yankees posted their first two-game winning streak in 2 1/2 weeks.
Cano's opposite-field hit ended what began as a neat duel between Baltimore lefty Brian Burres and struggling Ian Kennedy.
Mariano Rivera (1-1), in the game earlier than usual as the Yankees convert Joba Chamberlain into a starter, pitched a perfect ninth. Rivera, Jose Veras and Kyle Farnsworth combined to shut out the Orioles.
Jim Johnson (0-2) relieved Burres and got the last out in the eighth. After Matsui singled, Johnson fanned Alex Rodriguez and Jason Giambi.
Girardi rushed from the dugout after plate umpire Chris Guccione ruled Giambi was out on a foul tip. Girardi certainly got his money's worth for his first ejection as Yankees manager - he twice threw down his hat and kicked it once, then kicked the dirt while finishing his rant with crew chief Tim Welke.
The crowd was still buzzing when pinch-hitter Bobby Abreu walked, and Cano followed with a single through the left side. Matsui ran hard the whole way, and slid in as catcher Ramon Hernandez jumped to grab Payton's throw.
It was Girardi's 100th career win as a major league manager, not that he was in the dugout to see the finish.
Burres gave up six hits over 7 2-3 innings while walking none and striking out five. Kennedy pitched four-hit ball for six innings.
Freddie Bynum hit an RBI triple for a 1-0 lead in the third, but Baltimore missed a big chance to get more.
The Orioles loaded the bases with one out, helped when Brian Roberts stole second - he made it despite falling down and getting caught in a pickle. Rattled early in a loss last month at Baltimore, Kennedy composed himself, striking out Nick Markakis and retiring Aubrey Huff on a routine fly.
The crowd, sensing the 23-year-old Kennedy needed a confidence boost, responded with a standing ovation and Rodriguez patted the pitcher on the chest while cutting across the diamond.
The Yankees made it 1-all in the fourth on singles by Matsui and Giambi and a sacrifice fly by Shelley Duncan.
