The Mexican, who last fought in November 2019, ended Smith’s unbeaten record to take his WBA super-middleweight world title, as well as the vacant WBC belt, to become a four division world champion.
The 30-year-old last tasted defeat against Floyd Mayweather Jr in 2013 and had since seen off Smith’s brother Liam in 2016 to take the WBO light middleweight title.
Speaking after the fight, he told DAZN: “My respects for Callum Smith, but as everyone labels me I’m the best in the world and it’s for something.
“This is one of the best nights for me, I have conquered the unified titles. One of the greatest nights I’ve had and I will go for more.”
And, in a message for Gennady Golovkin, who he beat in 2018, he said: “My short-term goal is to unify all titles at 168 pounds. Whoever’s there, let’s go get them.”
Alvarez and the Kazakh drew in 2017 and the Mexican scored a narrow win in Las Vegas a year on, and there is now speculation a trilogy may be on the cards.
Smith boasted a height and seven-and-a-half-inch reach advantage over Alvarez but the Mexican superstar was undaunted at being the smaller man, having beaten taller and rangier fighters on a number of occasions in the past.
Smith said: “I’m devastated. Listen, I never wanted to lose, I came here to win. It wasn’t my night.
“I don’t feel as dominant at 168 as I used to be.
“It could have been a better version of me tonight … he performed and was the better man.”
Additional reporting by PA.