"The end of the COVID-19 public health emergency marks a tremendous transition for our country, for public health, and in my tenure as CDC Director," Walensky wrote to President Joe Biden in her resignation letter.
"We have all benefited from her service and dedication to public health, and I wish her the best in her next chapter," Biden said in a statement.
"For 75 years, CDC and public health have been preparing for COVID-19, and in our big moment, our performance did not reliably meet expectations," she told CDC staff last summer.
Public health experts said Walensky wrestled with political and technical challenges during her tenure.
"Dr. Walensky was put into place at the CDC at a time when the agency was basically captive to politicians which clearly hampered her ability to lead," he said.