Pettitte (6-7, 5.46 ERA) lost four of his first five decisions this season, but has rebounded to go 5-3 in his last nine starts.
The 12-year veteran has won back-to-back outings for the first time this season and is coming off a 9-2 victory over the Chicago Cubs on Tuesday in which he gave up one run and struck out five in seven innings.
“Any time you win, it’s nice—especially the way the year has gone so far,” Pettitte said. “Like I’ve been trying to say all along, I don’t know what … I can put my finger on, what I’ve been doing wrong. It just hasn’t happened.”
Pettitte is 5-0 with a 2.60 ERA in his last six starts against the Royals and hasn’t lost to them since a 3-0 defeat on Aug. 18, 1999 while a member of the New York Yankees.
He is 10-3 with a 3.04 ERA lifetime versus Kansas City.
If Pettitte produces results like rookie Taylor Buchholz did in a 7-2 win Saturday, the Astros (36-33) would clinch their fourth consecutive series victory.
Houston, which opened the series with a 7-2 loss to former Astros pitcher Scott Elarton on Friday, got six strong innings from Buchholz and three hits apiece by Mike Lamb, Lance Berkman and Adam Everett to improve to 9-2 in its last 11 games.
Everett is batting .333 (12-for-36) over that span.
“He’s not flashy, that’s what’s deceptive about him, he’s more of a (former Baltimore Orioles infielder Mark) Belanger-type shortstop,” Astros manager Phil Garner said. “He’s very, very solid.”
Third baseman Morgan Ensberg went 0-for-2 with three walks in his first start since bruising his shoulder while diving for a foul ball on June 9 against Atlanta.
Ensberg is batting .253 with 18 homers and 39 RBIs in 62 games.
The Royals (18-49) have lost six of their last eight games and seek their first series win in their last five when another former Astros pitcher, Brandon Duckworth (0-1, 3.18), starts Sunday.
Kansas City has not won a series since it took two of three at Oakland from May 29-31.
Duckworth made his first major league start in nearly 14 months Tuesday after he was acquired from Pittsburgh for cash considerations two days earlier.
The right-hander pitched well in his Royals debut, allowing two runs and striking out six in 5 2-3 innings, but wound up on the losing end of a 4-1 defeat against the Los Angeles Angels.
“I felt good going out there and giving the team a chance to win,” said Duckworth. “I felt I did an all right job in limiting any damage that could occur, but at the same time I’m disappointed that we lost.”
Duckworth, who spent his first three seasons with Philadelphia before he was traded to Houston in November 2003 for current New York Mets closer Billy Wagner, went 1-3 with an 8.08 ERA in 26 games with the Astros from 2004-05.