Castro, 53, was found Tuesday night at Correctional Reception Center, spokeswoman JoEllen Smith said. Upon finding Castro in his cell, facility staff tried to resuscitate him before he was taken to Ohio State University Medical Center where he was pronounced dead at 10:52 p.m.
Prison officials say Castro was housed in protective custody by himself with well being checks conducted every 30 minutes.
Castro, a former school bus driver, was sentenced to life in prison without parole plus 1,000 years for kidnapping Michelle Knight, Amanda Berry, and Gina DeJesus between 2002 and 2004 and imprisoning the women for more than a decade in his Cleveland home.
Castro pleaded guilty to 937 counts, including kidnapping, rape, assault and aggravated murder. The plea deal spared Castro the death penalty because he was accused of the aggravated murder of a fetus after forcibly causing an abortion in one of his victims that he is accused of impregnating.
The women escaped on May 6 after Berry forced her way out of the house, shouting to neighbors for help. The home was torn down last month as part of the plea deal.
Castro shocked the world at his sentencing last month by saying he was "not a monster," "lived a normal life" and had "consensual" sex with the three women he held captive. His statement came after Knight confronted him for the "hell" she endured in his house for 11 years.
Prison officials say more information will be provided after a thorough investigation of the incident.