"I'm a legend killer - I just finished B-Hop, maybe Roy Jones is next."
The bout was witnessed by more than 14,000 fans at the Thomas & Mack Center, the majority of them Welsh, and a galaxy of celebrities, including Jay-Z, Beyonce, Arnold Schwarzenegger and Catherine Zeta-Jones.
Welsh legend Tom Jones sang Land Of My Fathers (Mae Hen Wlad Fy Nhadau), and the Calzaghe fans, unlike the Ricky Hatton fans before his fight with Floyd Mayweather last December, respected the American anthem.
Hopkins's right hand had been one of the major talking points ahead of the clash and, sure enough, it had Calzaghe sprawling 70 seconds after the opening bell, stunning the partisan crowd into silence.
Calzaghe is delighted to achieve his goal
Calzaghe's legs looked stiff when he got to his feet, but he rallied and managed to make it through the round, although not without picking up a cut on the bridge of his nose.
Calzaghe, making his American and light-heavyweight debut, landed with his first meaningful shot in the second round, a chopping left, but Hopkins continued to pick him off on the way in and the Welshman looked very wary of letting his hands go.
The great Roy Jones Jr had warned Calzaghe ahead of the fight not to lower his work-rate and play into Hopkins's hands, but Calzaghe looked to be doing exactly that.
Hopkins landed with another couple of big right hands in the third and the fight was in danger of running away from Calzaghe, and Hopkins again controlled rounds four and five on the back foot, landing before gliding out of range or tying Calzaghe up on the inside.
I'm a legend killer - I just finished B-Hop, maybe Roy Jones is next
Calzaghe landed with a decent left at the start of the sixth and had more success during a wild exchange at the end of the round, sending home a big left cross.
The Welshman really began to step it up and outwork Hopkins in rounds seven and eight, although Hopkins, despite fighting on the back foot, never really looked in any trouble.
Calzaghe found Hopkins with a crisp left-right combination at the beginning of the eighth and found his rival again in the closing stages of the round with a crunching left.
But Hopkins, despite throwing considerably fewer punches, was still having success of his own on the counter, gliding out of range and trading with Calzaghe when called upon.
Calzaghe climbed off the canvas for the third time in his career
Hopkins showed all his experience in round 10, crumpling to the canvas after a low blow and taking a full two minutes to recover, to boos and catcalls from the Welsh contingent.
The American measured Calzaghe up with another trademark right when he was finally ready to return to action, and looked as though he had done enough to nick the round.
Calzaghe got Hopkins's attention with a huge left cross in round 11 before Hopkins folded again after what appeared to be another low blow, although replays showed it landed just below the waist-band.
With the fight still in the balance in most people's minds, the 12th and final round was fast and furious, but it was Calzaghe who again did the lion's share of the work and his fans were certain their man had done enough when the final bell sounded.
Judge Adalaide Byrd scored the fight narrowly for Hopkins, judge Ted Gimza gave it to Calzaghe, but Chuck Giampa, to the dismay of most of the watching media, awarded Hopkins only three rounds.
Hopkins was defiant in defeat, implying the decision should have gone his way.
"Look at my face, I don't have a bruise. I busted him up," said Hopkins.
"I took a guy to school who was undefeated.
"The whole world knows I won this fight. I controlled the pace like a true veteran."
Calzaghe can now look forward to a fight with Jones Jr later this year, while Hopkins, if he is true to his word, will slip into retirement.
This page is best viewed in an up-to-date web browser with style sheets (CSS) enabled. While you will be able to view the content of this page in your current browser, you will not be able to get the full visual experience. Please consider upgrading your browser software or enabling style sheets (CSS) if you are able to do so.