The Madison Square clash on November 8 will be both the first defence of his new light-heavyweight crown - and the last fight of his career.
The boy from Newbridge was last year also crowned BBC Sports Personality of the Year, seeing off fellow boxer Ricky Hatton and Formual One speed king Lewis Hamilton in the process.
Here we look back at Calzaghe's top 10 fights in an amazing career which has spanned 15 years.
AMERICAN fighter Jeff Lacy may have survived until the 12th round but he ended up a battered, bruised and bloodied figure.
This was a model peformance by Newbridge boy Calzaghe as he unified his WBF super middleweight title and grabbed Lacy's IBO title.
Calzaghe took the fight 119-105, 119-107, 119-107.