Victory was all the sweeter for the 24-year-old American who had lost a big chunk of his career due to a ban for missing drug tests and two wrist surgeries in 2023.
"It means the world," Brooksby said after his 6-4, 6-2 win over second seed Tiafoe.
"It was one of my biggest goals ever since I have been a professional tennis player. It means a lot to have my first one. It's probably the best week of my life."
Having come into the tournament at number 507 following the major disruption of his career, Brooksby also became the third-lowest-ranked champion in the tour's history since 1990.
He was hit with an 18-month ban in October 2023 for three "whereabouts failures" in a 12-month span but had the suspension reduced to 13 months on appeal at the Court of Arbitration for Sport after disputing the second missed test.
Hampered by injuries during and after the ban, he finally made his return to tennis at the Australian Open earlier this year and lost to compatriot Taylor Fritz in the first round.
Brooksby persevered and saved multiple match points in three of his matches to prevail in Houston.
"I've had a lot of different life adversity, whether it's on the court or off the court," Brooksby said.
"So I think it makes these situations... like, I still get nervous about them and somewhat tense for sure, but it gives you a different perspective once you've had to face other difficult things in life.
"I'm just someone who hates to lose and loves to win in general - obviously tennis being most important, but even in other games, and that's just how I'm wired as a person.
"I just really love winning, so that transfers over into when I'm in tough positions and maybe you should lose in those situations, that I'm able to at least find a way out of it."
