"He deserved a better fate," manager Brad Mills said of Lyles. "He threw the ball extremely well, and then they got some baserunners and things kind of got away."
With men on the corners, Lyles issued a walk and two run-scoring singles before getting the first out of the inning on a sacrifice fly by designated hitter Adam Dunn. Lyles blamed the inning entirely on himself and not the two misplayed balls that began the rally.
"I didn't make pitches, I put guys on base when I shouldn't, and when they hit the ball, it wasn't at someone," Lyles said. "The fifth inning's due to me, and we lost that game because of that fifth inning."
Lyles issued two walks and four hits in the inning. His afternoon concluded after an RBI single by Alex Rios.
"The first four innings were real good," Mills said. "I thought Jordan threw the ball well, and it would have been nice if we could make that play in the fifth and not allow those extra baserunners. You can't give teams, especially good teams, extra outs."
The 21-year-old starter went 4 1/3 innings, allowing seven hits and three walks. Lyles (1-2) pitched a season-low 4 1/3 innings, and failed to strike out a batter for the first time this year.
He hadn't allowed a player to reach scoring position until the breakout fifth, when his promising start came to an abrupt end. The loss followed Lyles' best start of the season, when he allowed just two runs in seven innings to earn his first win of the year against the Reds on June 3.
"We were both getting back out there in a short amount of time, and I just let the fifth inning blow up on me," Lyles said.
White Sox second baseman Gordon Beckham provided a two-run single in the fifth, and added another RBI single an inning later off of Xavier Cedeno, who stranded two runners in the fifth in relief of Lyles.
The White Sox continued pouring it on late. Dunn stretched the lead to double digits with a grand slam off of reliever Rhiner Cruz in the eighth inning.
Houston's five pitchers combined to allow 17 hits. Brandon Lyon, who hasn't allowed a run in 11 lifetime appearances against the White Sox, was the only reliever not to surrender a hit.
The Astros managed just four hits in eight innings off of Sale (8-2), who threw at least seven innings for the fourth straight start.
"Bouncing back after a loss is always important," Sale said. "You don't want to go into a skid or anything like that. Just coming out every day and being ready to go, that's the goal of every game that I start -- leave my team in the game and give them a chance to win."
Shortstop Jed Lowrie provided one of the few hits off of Sale on a comebacker that ricocheted off the pitcher's leg in the sixth. Sale stayed in the game and stayed in his groove, retiring J.D. Martinez on the next at-bat.
Sale didn't allow a hit in his final two innings of work, lowering his league-leading ERA to 2.05 and extending his scoreless innings streak to 15.
"He's a good pitcher," Mills said. "You just look at what he's done so far. In the month of May he was pretty outstanding, and he was pretty outstanding today."
Lowrie took advantage when Sale left, launching a solo home run off of White Sox reliever Zach Stewart to begin the ninth inning. Lowrie has homered in three straight games, and has hits in six of his first seven games in June.
The last Houston shortstop to hit home runs in three consecutive games was Andujar Cedeno in 1994.