Britain's Amir Khan will fight Mexico's Saul Alvarez for the WBC world middleweight title on 7 May in Las Vegas.
Khan, 29, a former light-welterweight world champion, has not fought since outpointing Chris Algieri in New York in May.
Alvarez, 25, beat Miguel Cotto by a unanimous points decision to claim the title in Las Vegas in November.
Alvarez has lost once and won 46 of his 48 fights.
The fight has been set at a catchweight of 155lb, eight more than Khan weighed in victory against Algieri and a jump of two weight divisions.
The usual weight limit for middleweight is 160lb, but Alvarez's last few fights have had the same weight stipulation.
The announcement also rules Khan out of a fight against IBF welterweight champion and domestic rival Kell Brook at Wembley on 4 June.
"I know Canelo fights the best and wouldn't pass up the opportunity to face me like others have," said Khan.
"My goal is to always fight the biggest names and the best fighters. That is why I'm excited for this fight.
"I know I have the speed and ability to beat him and will give my fans what they deserve."
Alvarez said he was looking forward to taking on Khan.
"Amir was a decorated amateur, a two-time world champion and is in the prime of his career," he said. "Fans are in for a great fight."
Khan has won 31 and lost three of his 34 professional fights.
BBC Radio 5 live boxing correspondent Mike Costello:
"There was not a word of speculation this fight was in the making. Only last Thursday, promoter Eddie Hearn was telling me how negotiations for Khan to fight Brook had made slight progress.
"What is happening for Khan is much bigger in global terms. His career for the past year has been on hold. Suddenly he has a chance, an outside chance, to become a superstar.
"He has been constantly chasing the big names for the past few years and finally the patience has paid off. This is a big step up in class. Alvarez has lost only once and that was to Floyd Mayweather."