Hughes himself started the season with a back issue and will make his first home start Saturday with the Yankees in search of a fifth straight win in the middle game of a series with the Baltimore Orioles.
Pettitte will be pushed back to Tuesday or Wednesday, with Hughes (0-1, 6.75 ERA) going Saturday instead of Sunday.
Hughes, who began 2013 on the disabled list, allowed four runs over four-plus innings in an 87-pitch outing in an 8-4 loss at Detroit last Saturday in his season debut. It's not hard to figure out what manager Joe Girardi wants to see from him now.
"Reduce the amount of pitches in the first five innings so we can get some length out of him and just build off his last start," Girardi said.
Hughes gave up a major league-high 22 homers at home last season. Five Orioles homered off him in five overall 2012 starts, although one of them - Mark Reynolds - is no longer with Baltimore.
The Yankees right-hander went 2-2 with a 3.99 ERA in those outings. The last one came in Game 4 of the division series when he allowed a homer to Nate McLouth for his only run over 6 2-3 innings with eight strikeouts in a 2-1, 13-inning loss.
After failing to homer Friday for the second time in 2013, the Orioles (5-5) will start Jason Hammel (1-1, 4.97), who was 0-1 with a 3.18 ERA in outings in Games 1 and 5 opposite New York ace CC Sabathia in last year's postseason.
Hammel hasn't fared as well in the regular season against New York, going 1-3 with a 5.53 ERA in eight starts. The right-hander yielded four runs over 6 2-3 innings Sunday in a 4-3 home defeat to Minnesota.
Sabathia proved to be Baltimore's nemesis once again in New York's 5-2 victory Friday. The left-hander eliminated the Orioles in Game 5 last year and struck out nine and allowed both runs over eight innings this time.
The Yankees (5-4) were aided by a strange series of events in the bottom of the seventh inning and then the top of the eighth.
"Just missed it,'' Jones said. "You could say it's rain. You could say it's cold. You could say anything, wind, you could say whatever you want. I was there. Didn't catch it. Cost my team the game.''
In the eighth, the first two Orioles singled before Manny Machado lined the ball on one hop to second baseman Robinson Cano to trigger a bizarre triple play.
Kevin Youkilis has hit safely in all nine games for New York, going 14 for 33. He's 1 for 9 against Hammel.