The 27-year-old Johnson won his second ATP Tour title, and became the seventh American to win the event since it moved to Houston in 2001. He also won a grass-court title last summer in Nottingham, England.
The fourth-seeded Johnson beat two former champions, Fernando Verdasco (2014) in the quarterfinals and American Davis Cup teammate Jack Sock (2015) in the semifinals, to reach his first final on U.S. soil.
The 29-year-old Bellucci, seeded eighth, lost his first ATP final in five tries. He won four three-set matches in four days before falling in the final.
Johnson was hobbled by cramps serving at the end of the third set, but - coaxing a backhand return error from Bellucci on a serve he barely hit - was able to get off the court and receive a brisk right-thigh massage from an ATP trainer. Players aren't allowed timeouts for cramps. Johnson appeared fine in the tiebreaker, the first to decide the championship in tournament history.
Johnson won NCAA singles titles for the University of Southern California in 2011 and 2012.