Scott Eby, 52, was serving a life sentence at the Menard Correctional Center in downstate Illinois.
Fox vanished from her Wilmington home in June 2004. Her body was later found in a creek four miles away.
Her father, Kevin Fox, was wrongfully arrested but was exonerated eight months later by DNA evidence.
RELATED: Who killed Riley Fox? How FBI's hunt for Wilmington girl's killer revealed major mistakes
In 2010, Eby confessed to the murder, saying on the night Riley disappeared he was breaking into homes around Wilmington. The Fox's backdoor lock already had been broken, and Eby told the FBI he just walked in.
Once inside, Eby said he couldn't find anything of value to steal.
"I was getting ready to leave and I looked back, and, I don't know, for some reason, I just fixated on that little girl," he told the FBI.
Eby said he brought Riley to Forsythe Woods, where he eventually sexually assaulted her in the park's bathroom and he told the FBI he decided to kill her after a bandana he'd worn to cover his face slipped off.
READ MORE: Wilmington man cleared after accused in daughter's 2004 death dies in head-on crash in Arkansas
Authorities said Fox had been sexually assaulted, bound and gagged. Her murder was later determined to have been from drowning.
Eby was already in prison for a different sexual assault when he confessed.
In 2010, Eby was charged with first-degree murder and predatory sexual assault. He pleaded guilty and was sentenced to life in prison without parole. In a victim impact statement to Eby during his sentencing, Melissa Fox spoke directly to him.
"I came to face you ... so you would know how important standing up for Riley was to me," she said. "She was defenseless that night, and that makes you a coward and a monster."
The Will County Sheriff's Department has not released Eby's cause of death. He died Thursday.
ABC News contributed to this report