Sabathia looks to make the Colorado Rockies a victim for the second time in that stretch in the finale of a three-game series Thursday in Denver.
New York is a baseball-best 40-19 in interleague play since the start of 2010 after beating Colorado 3-2 on Wednesday. Vernon Wells hit a two-run homer and pinch-hitter Brennan Boesch had an infield RBI single in the ninth for the Yankees (19-13), who had lost three of four.
Wells even played third base in the final inning for the first time, making a play on a grounder.
"That was one of the cooler moments of my career," the 34-year-old Wells said.
A major reason for New York's interleague success has been the performances of Sabathia, who is 9-1 with a 2.40 ERA in his last 11 starts versus the NL. He has the second-most interleague victories in the past three-plus years behind Detroit's Justin Verlander (10).
Sabathia (4-3, 3.31 ERA) was stellar the only time he faced the Rockies since joining New York, allowing one run and striking out nine in eight innings of an 8-3 victory June 25, 2011.
The left-hander, though, is coming off his shortest outing since opening day, and frustrations seemed to boil over with home-plate umpire Jordan Baker. Sabathia allowed both runs and eight hits in six innings of a 2-0 loss to Oakland on Friday.
Though Sabathia exchanged words with Baker in the third inning, manager Joe Girardi felt he pitched well despite giving up a home run on the first pitch of the game.
"He only gave up two runs, and he gave up one before he got an out," Girardi said. "They fouled some pitches off. They got in some long counts, which made him throw a lot of pitches in the sixth inning, but I thought he threw OK."
Troy Tulowitzki, who went 2 for 3 off Sabathia in 2011 in their only matchup, entered Wednesday's contest as a pinch hitter in the eighth inning after being held out of the starting lineup for a second straight game due to leg soreness.
Though Tulowitzki, hitting .348, said he felt good running before the contest, manager Walt Weiss decided to sit him again given the poor weather conditions. The shortstop was hit with a pitch and promptly removed for a pinch runner.
"He's fine," Weiss said. "Curveball, just got him I think part of his helmet and might have hit his neck a little bit. Didn't hit him square."
Todd Helton hit a two-run homer for the Rockies (19-14), who have gone 6-10 since opening the season winning 13 of 17. They'll turn to starter Jeff Francis in hopes of closing the series on a positive note, though he's struggled of late.
Francis (1-2, 7.27) hasn't pitched more than five innings since his season debut, posting a 9.00 ERA over his last five starts. He gave up four runs in five innings of a 7-4, 10-inning loss to Tampa Bay on Friday.
"I felt like if I'd made some better pitches, we could have been ahead and won," Francis said. "I missed with a couple of pitches and it cost me some runs."
The left-hander won his only start against the Yankees on June 20, 2007, allowing one run and striking out nine in seven innings of a 6-1 victory.