On Thursday, Louisiana Governor John Bel Edwards saidhe accepted the resignation of Walters, who has served as the state's Department of Children and Family Services (DCFS) secretary for more than six years, reports Xinhua news agency.
In the past four months, three children have died after warnings to the agency, including a two-year-old overdosing on fentanyl, a media report said.
Three reports had been made to the DCFS about his family before the toddler's death in June. However, the agency never made contact with the family or tried to remove him from their care, said the report.
Then, on October 31, a 20-month-old child died from acute fentanyl toxicity. Ten 10 days before his death, an anonymous caller had warned that his family members were using drugs around him.
The corpse of another two-year-old boy was found stuffed in a duffel bag inside a trash can this summer, also after DCFS had been warned about and had opened an investigation into his family.
Walters wrote in her resignation letter that working for the DCFS has become increasingly difficult amid a national fentanyl epidemic.
The DCFS has been trapped in crisis in recent years as reports of abuse and neglect across Louisiana are rocketing, according to the media report.
Out of more than 400 vacancies it has, 174 are in the agency's child welfare department.
Louisiana, like many US states, is facing major child welfare challenges, said the governor.
"Those issues include staff retention, high worker caseloads, increased substance and domestic abuse and, sadly, the tragic deaths of innocent children," he added.
IANS, Xinhua