Second-year quarterback EJ Manuel threw as many interceptions as he did touchdown passes, and the Bills fell 23-17 to the Texans for their second straight loss.
They had a solid defensive performance that included forcing three turnovers, including two interceptions but failed to overcome another flat performance by Manuel and the rest of the offense.
"We concentrate a lot on progression with the quarterback," Bills coach Doug Marrone said. "But ... we need progression in three areas: making sure we protect well; making sure we catch some of them; and making sure we throw some of them to better spots."
Under pressure all afternoon, Manuel finished with 225 yards passing with two touchdowns and two interceptions for the Bills (2-2).
"Very disappointing," Manuel said. "We weren't clicking like I think we needed to. Just have to move on, process it and learn from it."
Manuel's first interception was a momentum-changer.
Houston (3-1) was down by three in the third quarter and Ryan Fitzpatrick had just thrown a second interception when JJ Watt, Houston's 6-foot-5, 289-pound star defensive end, returned an interception 80 yards to put the Texans up 14-10.
The second was also costly.
Buffalo was driving late when Darryl Morris picked off Manuel at the Houston 15 to secure the victory.
However, Marrone didn't place all the blame on Manuel.
"There were some balls that we could have caught during that game," Marrone said. "That's why I say it's a combination of those three things."
"It's not just a one player fix," he continued.
Manuel got the Bills within 20-17 when he hit a wide-open Mike Williams for an 80-yard touchdown with about nine minutes left.
Randy Bullock had a 41-yard field goal in the third quarter and added field goals of 55 and 50 yards in the fourth for Houston.
Defense kept the Bills in the game.
"We hear a lot of stats saying if you get three turnovers or four turnovers your chance of winning are high, but anything can happen in one play," Bills safety Aaron Williams said.
That play came at the hands of Watt, whose interception came three plays after Bradham's pick when he got his hands on the pass to tip it to himself. Kareem Jackson blocked Manuel at the start of the return and Watt went all the way to the end zone.
"We've got to get that throw over his head," Marrone said. "He made a play, and a key of ours was to make sure he wasn't going to make that big disruptive play prior to the game, and he did, and he made a lot of plays."
A TD reception by DeAndre Hopkins capped the first drive where the Texans mustered any offense, and they had negative yards rushing until late in the second quarter.
"They made the plays when it counted," Aaron Williams said. "We didn't."
The Bills took advantage when Sammy Watkins got in front of Morris for a 5-yard reception to make it 10-0. Fred Jackson had a nifty 14-yard run up the middle in that drive as he faked one defender before making three other Texans miss.
The Texans gave the ball right back when Leodis McKelvin intercepted Fitzpatrick on Houston's next play. McKelvin was behind Hopkins and out jumped him. It was his second interception this season.
NOTES: Houston's Arian Foster played after missing last week with a hamstring injury and said he wasn't "100 percent" healthy. He was limited to eight carries for 6 yards, but gained 55 yards on seven receptions. ... Bradham and defensive tackle Kyle Williams left with knee injuries and didn't return. Marrone didn't have an update on their condition after the game.
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