Burnham will complete his second term leading the state's 152 school districts, timing his departure to the end of the budget year.
He first led the state's K-12 schools from 1992 to 1997. After Hank Bounds left to become commissioner of higher education, Burnham was recalled by the state Board of Education in 2009. His second tour in the job took place in a period when the state's schools have struggled with tight budgets and strived to meet higher accountability standards.
"I have served passionately for 43 years as an educator striving to make positive changes and to provide better opportunities for children," Burnham said.
No details were immediately announced as to whether state board members would appoint an interim successor, or how they would choose a permanent replacement.
Burnham served as dean of the School of Education at the University of Mississippi between stints as state superintendent. He earlier served as superintendent of Henderson County Public Schools in North Carolina and Biloxi Public Schools.
In his second stint, he and appointed members of the state Board of Education have worked to improve student achievement and ratchet up standards on local school districts.
The state superintendent currently makes $307,000 per year, an amount set by state law.
Read more in Saturday's NEMS Daily Journal newspaper.