It was the second consecutive defeat in the three-game series for a Mets team that looks to avoid the sweep in a Wednesday afternoon finale.
Niese served up a first-inning two-run homer to Astros shortstop Jed Lowrie that hit the foul pole in left field and a second-inning three-run blast to catcher Chris Snyder, the team's No. 8 hitter who entered the game with a .121 batting average and no homers.
It was a 5-0 hole from which the Mets couldn't climb.
"That Lowrie pitch, I regret throwing him a fastball there," Niese said. "I wanted to throw him a curveball. I threw it up and in on him and he got it. And then the Snyder one, he just ambushed me first pitch and he got that one, too.
"It was just a sinker that stayed up," said catcher Josh Thole. "I think when that happens, it just takes the wind out of you a little bit."
"It was a two-strike count, so I'm just trying to react at that point," Lowrie said of his third homer this season. "You start guessing with a guy like that with a good curveball and he's liable to beat you. I reacted to a fastball up and I was able to hit it off the pole."
"Other than that I felt great," Niese said. "It's just one of those games where it gets away from you early. You've just got to put it in the past and get ready for the next start."
Niese broke a string of four consecutive quality starts, which tied the longest such run of his career.
He was pinch-hit for in the Mets' two-run fourth inning.
"When you're in a game where you're down five and you have a chance to tie it, you have to take the opportunity," manager Terry Collins said of the move. "We didn't have another chance the rest of the game to tie it. So I took my chances then."
Lucas Duda, who continues to battle flu-like symptoms, got the call off the bench with two on and two out. He was the potential tying run in the inning, but struck out looking.
For the Mets, the fun often begins after two outs. Over seven previous games, New York scored 20 runs with two outs and 47 runs with two outs for the year, the second most in the Majors.
The Mets added all three runs on Tuesday with two outs, chipping away with two runs in the fourth and another in the fifth.
It began in the fourth with consecutive two-out RBI singles from center fielder Andres Torres and Thole that plated second baseman Justin Turner, who doubled, and right fielder Scott Hairston, who drew a walk.
A two-out RBI single by Hairston in the fifth trimmed Houston's lead to 5-3. Turner scored on the clutch hit after coaxing a two-out walk and moving into scoring position on a David Wright single.
Wright went 2-for-4, extending his hitting streak to eight games, dating back to April 24. During the streak, Wright is hitting .429 (12-for-28) and has reached base safely in 20 of 21 games this season.
But the chances were few and far between for New York. Astros starter and winner J.A. Happ (2-1) pitched into the seventh, allowing three runs on six hits while striking out seven.
"From a left-handed standpoint, I just felt like the ball was on me pretty quickly," said Thole. "My first at-bat, it just seemed like it was over before I even felt like I was even up there -- just good late life [on his pitches]."
The Mets are 2-3 on the six-game road trip and are 5-6 away from Citi Field. New York will play 14 of its next 21 games on the road.
"Any time you lose two ballgames, especially like the one last night, it's tough," Thole said. "But you've got to move on. [On Wednesday] we play at 1 [p.m. CT], so we can't think about this one too long."