Bautista floored Mendoza with a left hook to the head in the middle of the sixth round, and Mendoza was counted out by referee Danrex Tapdasan.
It was a strong performance for Bautista, who retained his International Boxing Federation (IBF) international featherweight title in the process.
Bautista showed patience throughout the bout, refusing to get caught in a brawl with Mendoza who has a reputation for being a knockout artist.
But it was Bautista who showed his power first, sending Mendoza to the canvas twice in the first round with quick left straights.
The Mexican fighter started to bleed in the second round, but still continued to challenge "Boom Boom." He was not very effective in his offensive attack, however, opting to go for wild, swinging punches that often hit nothing but air.
Bautista also showed his ability to take a punch as he decided to stay in front of Mendoza for most of the bout. Despite getting tagged with some punches from the Mexican, "Boom Boom" stayed up right and was able to counter with short punches to Mendoza's head.
The fight was marred with several timeouts, however, as referee Tapdasan warned both fighters for low blows. He also stopped the clock to give Mendoza time to get checked out by the ringside doctor.
For Mendoza, it was the first loss of his career and his first fight that went past the fifth round. He had won each of his past 17 fights via knockout.
Bautista improves his record to 32 wins and 2 losses, with 24 wins coming by knockout.
Undercard
In the main undercard fight, Genesis "Azukal" Servania won a dominant unanimous decision victory over Marcos "Geraldito" Cardenas.
All the judges scored the bout for Servania: 98-90, 97-91 and 97-91.
It was the first loss for Cardenas, who tried to use his longer reach throughout the bout to keep Servania at bay. But the Filipino boxer showed patience in stalking Cardenas, and was able to get inside and pepper him with short hooks.
A strong left hook from Servania sent Cardenas to the canvas late in the first round, but the Mexican boxer bounced back quickly. Cardenas would go down again in the fourth round, however, after a flurry of punches from "Azukal."
Cardenas now has a 19-1 win-loss record, while Servania improves to 16 wins with 7 knockouts.
The other undercard bout saw Filipino Rocky Fuentes score a second-round technical knockout victory over Lookdiaw Tor Buamas of Thailand.
Buamas, a former World Boxing Council International silver light flyweight champion, could not withstand a series of hooks from Fuentes in the second round, prompting the referee to stop the contest.
