The fight is a rematch from a fight in September 2017 that ended with a controversial draw.
That showed at Friday's weigh-in, when the two fighters had to be separated in their only face-to-face appearance before the fight.
An ill-tempered confrontation before several thousand fans at the T-Mobile Arena saw a minor scuffle after the two fighters came together after stepping on the scales.
The courageous Armenian lasted all of four minutes and 53 seconds before being clobbered into submission as Golovkin made a statement to his rivals in the division with yet another imposing knockout.
Kazakh fighter Golovkin, the defending WBA, WBC and IBO champion, weighed in slightly heavier at 159.6 pounds (72.4 kgs). But it was a tough, competitive matchup that delivered in other ways even without a victor at the end.
"These stories about contaminated meat are nonsense", Golovkin said, claiming to have seen injection marks on Alvarez's body in photos of his opponent.
"I'm bothered by all the stupid things they've been saying and I've been using it as motivation in my training for this fight".
The most popular fighter in his native Mexico, Alvarez has taken a hit from some of his rabid fans both for testing positive and for not fighting more aggressively.
Regardless, he was suspended by the Nevada State Athletic Commission before being handed a six-month ban, backdated from February, forcing him to pull out of the agreed rematch with Golovkin. "In order to win a fight you have to want to win a fight".
The first fight delivered not only in the ring but at the cash register, with a $27 million gate and 1.3 million pay-per-view buys.