Mysterio quickly moved into a feud with the United States Champion John "Bradshaw" Layfield. The rivalry kicked off after JBL, celebrating his U.S. Championship win, stated he deserved the World Heavyweight title. This feud saw Mysterio face off against three opponents chosen by JBL in the three weeks leading up to their title match at Judgment Day. Mysterio was defeated by Mark Henry and The Great Khali in separate non-title matches before wrestling Kane to a "no contest"; Mysterio retained his title against JBL at Judgment Day. The feud intensified when JBL lost the United States Championship to Bobby Lashley five days later on "SmackDown!" after being tricked by Mysterio to take on all comers like Mysterio himself had. JBL vowed that if he did not win his rematch against Mysterio, he would quit SmackDown!. In their main event match, Mysterio retained the World Heavyweight Championship, causing JBL to leave SmackDown!, until ECW One Night Stand, when he announced his return as a color commentator. Mysterio was booked to defend against ECW wrestler Sabu at One Night Stand. In the weeks leading up to his title defense, Mysterio defeated Cruiserweight Champion Gregory Helms in a Champion vs. Champion match, and lost to Rob Van Dam at WWE vs. ECW Head-to-Head on June 7. At One Night Stand, Mysterio retained the title, after he and Sabu were ruled unable to continue following a triple jump DDT through a table by Sabu. Mysterio then retained his title in a match against Mark Henry, winning by disqualification after Chavo Guerrero handed Henry a chair and Mysterio acted as if he was hit, a tactic for which Eddie Guerrero was known.