After 52 years in journalism, Lehrer said that "there comes a time to step aside from the daily process, and that day has arrived."
Lehrer said he would still appear on Fridays to moderate the "Newshour's" weekly analysis feature with columnists Mark Shields and David Brooks.
The 76-year-old also said that he will continue to be involved with the program's producer, Arlington-based MacNeil/Lehrer Productions.
His exit, which will take place the week of June 6, ends the longest run of a national anchorman.
In addition to his PBS show, Lehrer is widely known for his role as the moderator of presidential debates.
The Associated Press contributed to this report.