The one-time punk idol will tread the boards playing Herod during a 50-city US tour of the show which was created by Andrew Lloyd Webber and Tim Rice.
Lydon, who was known as Johnny Rotten during his Pistols days, is an unlikely addition to the show which features pop acts such as Michelle Williams of Destiny's Child and JC Chasez of the former boy band 'N Sync.
However he had spoken in the past, possibly in jest, of his desire to be in the show. At a 2003 music conference he was asked whom he would like to portray in a movie.
He responded: "It would be Jesus Christ. And I'll do the musical too."
Lydon, 58, said of his involvement with the show: "I'm here to sing with the King of the Jews, who could ask for anything more?"
The singer was just 20 when he released the debut Sex Pistols single Anarchy In The UK, which opened with the line: "I am an anti-Christ, I am an anarchist."
Over the years he has gone from being the enfant terrible of punk to a familiar face to millions of TV viewers after taking part in I'm A Celebrity ... Get Me Out Of Here!, hosting wildlife shows and starring in TV adverts for butter.