It's back to the drawing board for the Patriots, who fell to 4-6 on the season following a 27-20 loss to the Texans on Sunday.
"It was a disappointing outcome for us today," New England coach Bill Belichick said. "We had some opportunities throughout the course of the game and just couldn't do enough with them."
Cam Newton completed 26 of 40 passes for 365 yards in the loss, but threw incomplete passes on back-to-back plays on third and fourth down on New England's second-to-last possession to hand the ball back to Houston.
While the Texans failed to pick up a first down and punted the ball back to the Patriots, their last-ditch efforts to tie the game also came up short despite a pair of completions to Ryan Izzo to pad the stats.
The Patriots ran the ball just 24 times as a team, despite the fact that Houston had the NFL's worst rush defense in the NFL entering play Sunday, surrendering an average of 167.4 yards per game on the ground.
Damien Harris, a week after setting a career-high with 121 rushing yards, had just 43 on 11 carries Sunday.
Harris had a 9-yard touchdown run to open up scoring with 6:52 left in the first quarter, but the Texans responded with a 3-yard touchdown pass from Deshaun Watson to Randall Cobb on their next drive to tie the game at 7-7.
A Nick Folk 45-yard field goal made it 10-7 New England midway through the second quarter before Houston took the lead on a 4-yard rush by Watson with 3:54 left in the half. The Texans increased their cushion to 21-10 just 0:10 shy of the break, when Watson threw a 6-yard touchdown pass to Keke Coutee.
Damiere Byrd caught his first touchdown as a Patriot, a dart from 42 yards away from Newton, with 8:14 left in the third quarter. It was the first touchdown pass Newton had thrown to a wide receiver with New England, slicing its deficit to 21-17.
Ka'imi Fairbairn and Folk traded field goals, with a Fairbairn 46-yarder giving Houston a 27-20 lead with 4:14 left.
The 365 yards Newton finished with were his second-most as a Patriot and fifth-most in his career. He completed six passes for 132 yards for Byrd, a career-high.
In his return to the lineup, N'Keal Harry caught five passes for 41 yards. James White was also more involved for the Patriots Sunday, catching six passes for 64 yards.
Newton didn't turn the ball over for a third straight game and didn't throw an interception for a fourth-straight week. But he had several balls batted down at the line of scrimmage again, including four by Houston defensive end J.J. Watt.
"He's J.J. Watt, what do you expect ... he's an All-Pro, perennial All-Pro," Newton said. "He's a Defensive Player of the Year, one of the best players in this generation."
New England returns home and will face the Arizona Cardinals next Sunday at 1 p.m.