The offense had 75 yards to go, and Stroud had one message for his offensive line.
"If you give me a little bit of time, I will make them pay," Stroud said.
Six plays later, Stroud triumphantly fired a winning, 15-yard touchdown pass to wide receiver Tank Dell to take the lead 39-37 with just six seconds left, the latest go-ahead touchdown pass in Texans team history.
Stroud's execution on the last drive set a record for passing yards by a rookie as he finished with 470 yards -- passing Andrew Luck (433) -- and five touchdowns with no interceptions.
"C.J. is different. He told us to stay poised and be ready, and he executed," Dell, who finished with two touchdowns and 114 yards, said. "He didn't panic. But we knew that out of him, and that's what he do."
Stroud's last drive propelled him into the record books in other categories, too. He became the sixth player in NFL history to record 450 pass yards and five passing touchdowns with no interceptions. He also became the first rookie with 400 passing yards with five touchdowns and zero interceptions.
"It makes it easy on everybody. No cap, that boy is a problem," left guard Tytus Howard told ESPN. "He's special. And to be doing all this as a rookie, the sky's the limit for him. We just got to do our job, keep giving time and we know he's going to deal."
Stroud finished the day with the most passing yards in a game this season. And before the winning drive, it appeared that a loss could have overshadowed Stroud's performance as he sat at four touchdowns and 395 yards.
Texans safety Jalen Pitre walked to the sideline disappointed after the defense allowed the go-ahead score. But Pitre quickly realized the offense had two timeouts and 46 seconds and believed the Texans would still win.
And Stroud proved Pitre correct.
"That's not even coachable. They said something about he did a veggie meter to check how much veggies are in your bloodstream, and they found all ice," Pitre said with a smile. "He's like that for real. No vegetables, straight cold-blooded. [He's] ready for the moment, bro. I was about to put my head down, and I said, 'No. We still got time.' And they then start driving. [Stroud threw to] Dalton [Schultz], Noah [Brown], Tank and Tank. And I'm on the sidelines, smiling again."
The No. 2 pick's performance followed a three-game stretch in which he averaged 196 passing yards and threw only three touchdowns as the Texans won only one game.
"[Offensive coordinator] Bobby [Slowik] was looking for us to answer the bell," Stroud said. "We know we should have been way better against the Carolina Panthers, and he did a great job. He told me this game, 'You got to make plays and be special. You're a special player, go be special.' And he put the ball in my hand, and I appreciate that."
Even in a last-second, crushing defeat, the Buccaneers were impressed by Stroud's performance.
"I'll tell you what -- C.J. Stroud doesn't look like a rookie to me," Mayfield said. "That guy, he's so impressive. Looks like a polished NFL quarterback. So hats off to him. He played extremely, extremely well today."
The Texans' win moved them back to 4-4 as they prepare for a tough test against the Cincinnati Bengals on the road.
But in Texans players' eyes, as long as they have Stroud, they believe they can win any game.
"That boy the truth," Texans running back Devin Singletary told ESPN. "He's a dog. Killer instinct and never wavered. It wasn't pretty at first, but he led us, and we rallied."
ESPN's Jenna Laine contributed to this report.