Gov. Bill Haslam announced Kate O'Day's resignation in a news release and wasn't immediately available to comment.
"She was concerned that she had become more of a focus than the children the department serves," Haslam said in the release.
The Republican governor last week defended O'Day's leadership, even after the agency told a federal judge it couldn't say with any certainty how many children died while in its custody.
DCS had been sued by The Tennessean, The Associated Press and 10 other news organizations to obtain case records of 151 children who died between January 2009 and July 2012 and had been the subject of state investigations of abuse or neglect.
Chancellor Carol McCoy ruled last month that DCS, which had claimed it was keeping the records closed to protect the children's privacy, had to release hundreds of pages from four cases to the news organizations after identifying information was redacted. A decision on whether more records were to be released is pending.
DCS has been under federal court oversight for more than a decade over problems in Tennessee's foster care system.
Less than two weeks ago DCS told a federal judge that it couldn't accurately count how many children have died in its custody, saying its tracking system had missed nine deaths in 2011 and 2012. The revelation and increasing calls for DCS to improve its performance have threatened to derail more than 10 years of work to resolve a long-running lawsuit over the agency's handling of foster care.
Thus far, officials have not been able to explain how DCS overlooked the nine deaths except to say that it was the result of human error.
Haslam named Commissioner Jim Henry, the head of the Department of Intellectual and Developmental Disabilities, to serve as interim commissioner of DCS.
O'Day had been commissioner since January 2011, when she was appointed by Haslam. Before that she was president and chief executive officer of Child & Family Tennessee in Knoxville.
Associated Press writer Erik Schelzig contributed to this story.