Castro, 52, is accused of kidnapping Amanda Berry, Gina DeJesus and Michelle Knight and holding them captive along with a 6-year-old girl he fathered with Berry.
A Cuyahoga County grand jury charged Castro with two counts of aggravated murder for purposely causing the unlawful termination of one of the women's pregnancies.
Castro is also indicted on 139 counts of rape, 177 counts of kidnapping, seven counts of gross sexual imposition, three counts of felonious assault and one count of possession of criminal tools.
Castro was being held on $8 million bail. He was briefly arraigned in May but did not speak. His attorneys have said he would plead not guilty to any indictment. He was monitored on suicide watch but has since been taken off.
Cuyahoga County prosecutor Tim McGinty said the indictment covers only the period from August 2002, when the first of the women disappeared, to February 2007.
Castro will be arraigned on the charges next week, and a trial judge will then be assigned.
Castro was arrested May 6 after Berry broke through a locked door, yelled to neighbors for help and escaped with DeJesus and Knight.
Berry, 27, told officers that she was forced to give birth in a plastic pool in the house so it would be easier to clean up. Berry said she, her baby and the two other women had never been to a doctor during their captivity.
Knight, 32, said her five pregnancies ended after Castro starved her for at least two weeks and "repeatedly punched her in the stomach until she miscarried," authorities said.
She also said Castro forced her to deliver Berry's baby under threat of death if the baby died. She said that when the newborn stopped breathing, she revived her through mouth-to-mouth resuscitation.
The women had vanished separately between 2002 and 2004, when they were 14, 16 and 20 years old.
Castro's two brothers were arrested with him but later were cleared of involvement in the case and were released.
The investigation was ongoing. When the indictment process is completed, the county prosecutor's capital review committee will weigh whether the case is appropriate for seeking the death penalty, a Cuyahoga County prosecutor said.
Castro is a former school bus driver. He was fired last fall.
The Associated Press contributed to this report.