He'll retire effective at the end of the state fiscal year June 30.
Burnham was superintendent in the mid-1990s when the Legislature passed the historic Mississippi Adequate Education Program to provide additional funding to all school districts and to enhance funding to the state's property-poor districts.
And he was rehired as the state's top educator in November 2009 in the midst of a historic downturn in revenue collections, making it difficult to fund the MAEP.
In a statement late Friday, the 65-year-old Burnham said, "I have served passionately for 43 years as an educator striving to make positive changes and to provide better opportunities for children. I sincerely appreciate the Mississippi Board of Education and the staff at the Mississippi Department of Education for their support throughout the years.
"I also greatly appreciate the support of policy makers, local superintendents, principals, teachers and parents."
Burnham did not confirm his future plans, but sources indicate he will work with the Oxford-based Barksdale Reading Institute on leadership training for local school districts.
Burnham was state superintendent from 1992 until 1997, but retired after an intense legislative session where the Adequate Education Program was passed. He said when he returned in January 2010 that his was worn out when he retired in the 1990s.
He served as dean of the University of Mississippi School of Education from 2004 until his second tenure as state superintendent. He also has served as local school superintendent in Biloxi and Henderson County, N.C.
He was hired the second time as state superintendent to succeed Hank Bounds, who become commissioner of higher education.
Senate Education Chairman Gray Tollison, R-Oxford, said he enjoyed working with Burnham this past legislative session and praised him for proposing tough legislation to deal with poor performing schools and with school accountability issues.
Former longtime House Education Committee chairman Cecil Brown, D-Jackson, said he was "very sorry to hear about Dr. Burnham's decision for the sake of the state, education and all of the schoolchildren. But it is probably good for Tom. It has been a tough period." He said Burnham called him at noon Friday to inform him of his decision to retire.
Brown said Burnham "labored" with the lack of state funding for local school districts.
"He heard from local superintendents about that," Brown said. Plus, Brown said the fact that the state board has had to take over eight school districts because of accreditation issues made his task even more difficult.
New Albany Schools Superintendent Charles Garrett, lauded Burnham's work.
"He's a great educator and a good friend to everyone who works in school districts,"said Garrett, who is retiring this summer to lead the Toyota-endowed Wellspring school. "He's been an outstanding leader."
Burnham has put Mississippi on the right course, Garrett said.
"I hope the state board continues with the plan in place and the Legislature supports them," Garrett said. "It's a long term plan to improve education in Mississippi."
There is speculation that working with the Legislature had become more difficult for Burnham. The state Department of Education has come under attack in recent years from some legislators who have complained about the agency's funding and the state's education attainment level.
"He is a professional. He could handle that," Brown said. "He has just given 40-plus years to education and is tired. He wants to do something else."
The tenures of superintendents of education in Mississippi have been relatively short. After Burnham left in 1997, there were three state superintendents before he returned in January 2010.
The Board has hired from within Mississippi's educational community at times and at other times has gone outside the state to hire the state's top educator.
"Tom was a superintendent's superintendent," said state Board of Education member Claude Hartley of Tupelo, who played a key role in hiring Burnham. "He did an excellent job as state superintendent. The board will have its work cut out replacing him."
Burnham was hired in 2009 for $307,000 annually, an amount set by state law.
Michaela Gibson Morris contributed to this story.