With American Garcia picking off the Mexican champion in the eighth round at Madison Square Garden, Salido came forward in an attempt to change the momentum and accidentally caught the bridge of Garcia's nose with his forehead, breaking it.
The scorecards easily gave the bout to Garcia - 79-70, 79-69, 79-69 - after he decked Salido four times, including twice in the first round.
"His speed was a problem and it was very hard to recover from the first knockdown," Salido said afterwards.
He was also floored in the third and fourth rounds.
Garcia is 31-0 after his triumph in the main event in New York while Salido moves to 39-12-2.
Salido, who had swelling under his right eye, was defending the title he won two years ago from Juan Manuel Lopez. He had defended it four times, including once against Lopez.
"I told everybody it was just another fight for me," Garcia said. "I'm not so worried about what's at stake. I just want to show everybody the fighter I am.
"I wanted to show all my skills and how good I can really be. I knew a guy like Salido would really test me and would allow me to do all that.
"Other fighters haven't done everything like they're supposed to, and they allowed me to work comfortably without doing so much. Salido made me do more, and allowed me to do a lot more."
'Mikey' is the brother of retired world champion Robert Garcia, who trains him.
"He fought exactly the way we trained," Robert said. "We trained for that for over two months and he executed the game plan exactly the way we told him.
"The punches that we practised are the punches that we hurt [Salido] with. The movements he did, really, everything he did in the fight, it was all done in the gym."
Elsewhere on the show, Kazakhstan’s Gennady Golovkin got his American dream well underway with a bloody seventh-round stoppage win over Gabriel Rosado to retain his WBA middleweight crown.
The 30-year-old hopes to gain a following in the USA and took a step in the right direction with a powerful 22nd knockout success over the Puerto Rican-American to move to 25-0.
Rosado’s compatriot Roman Martinez did retain his WBO junior lightweight title with a split draw decision against Mexico's Juan Carlos Burgos in his first defence.