The agency registered a case on the request of Bihar government and a further notification from Central government, a CBI official said.
Under pressure from the opposition, Bihar Chief Minister Nitish Kumar on Thursday recommended a CBI probe into the series of rapes that he described as "a heinous crime".
The agency official said: "The CBI has taken over the investigation of the FIR (First Information Report) of Mahila Police Station, Muzaffarpur registered on May 31 related to mental, physical and sexual exploitation of girl children residing at Children Home at Sahu Road in the town.
"The case has been registered against officers and employees of Balika Grih Sahu Road, Muzaffarpur."
The matter had come to light earlier this year when the Bihar Social Welfare Department filed an FIR based on a social audit of the shelter home conducted by a Mumbai-based institute.
The audit report stated that many girls at the shelter home had complained of sexual abuse. A special investigation team was formed to probe the complaints.
The NGO running the shelter home in Muzaffarpur was blacklisted and the girls were shifted to shelter homes in Patna and Madhubani.
Women staff members of the shelter home and Brajesh Thakur, who ran the NGO, were among those who were arrested by the local police in connection with the case.
A medical examination of 44 girls of the home revealed that 34 of them were sexually exploited. All of them are children, most of them between seven and 14 years old. The district police have arrested some officials of the home.
According to the Telegraph Calcutta, the girls said - in statements recorded before the special POCSO court - that they were tortured, starved, injected with drugs, and raped almost every night.
(With inputs from agencies)