The men, Ronald Washington and Karl Jordan, Jr., were indicted on charges of murder while engaged in drug trafficking, according to two law enforcement officials, who spoke on the condition of anonymity.
It was not immediately clear what role the two men played in the killing, but investigators believe Mr. Mizell was involved in the finances of the drug-trafficking operation.
“There was a beef — it didn’t go as planned,” one official said.
Federal prosecutors in Brooklyn plan to discuss the case at 2:30 p.m. in a news conference with other law enforcement officials.
Mr. Washington, 56, is currently serving a federal prison sentence for robbery. Mr. Jordan, 36, was taken into custody on Sunday and previously had gone to prison for shooting Mr. Mizell’s nephew.
Mr. Mizell, who was 37, was killed on Oct. 30, 2002. That evening, he had been playing video games in the lounge of a second-floor studio in Jamaica, Queens.
Two men entered the building, and one of them, who was wearing a mask, fatally shot Mr. Mizell in the head, officials had previously said.
Detectives explored several possible explanations for the shooting, including that it stemmed from a grudge against the rapper 50 Cent, who was a protégé of Jam Master Jay’s. That theory was later discounted.
Investigators who reviewed Mr. Mizell’s business and personal relationships struggled with finding a motive and wondered why someone might want to kill a man who had not embraced prominent rivalries with others.
Mr. Mizell had many admirers in Queens, and spent several years of his childhood in the neighborhood of Hollis, a neighborhood that has a rich hip-hop legacy.
He gained nationwide fame as the pioneering D.J. of the hip-hop trio Run-DMC, which included Joseph Simmons, known as Run, and Darryl McDaniels, known as DMC.
In the years before Mr. Mizell’s death, he increasingly embraced the role of a local talent scout, listening to demo tapes of 14- and 15-year-old rappers and making suggestions. In 2002, he founded the Scratch D.J. Academy, where students learned D.J. techniques.