NBC said Monday it would name a successor soon; someone whose duties will also include weekend work at NBC or MSNBC.
NBC bosses decided that a newsman whose primary duties were anchoring on the weekend was a luxury they could no longer afford.
Seigenthaler had been with NBC News for 11 years, joining after local news stints in Nashville, Tenn., and Seattle. He was named anchor of the weekend editions of "NBC Nightly News" in 1999.
NBC's weekend newscast tops its rivals in the ratings. During weekdays, "NBC Nightly News" has been eclipsed by ABC's "World News" during the past two months.
Seigenthaler announced his departure on Sunday night's show. He thanked NBC News and his viewers for being loyal.
"And thanks to my dear family," he said. "Finally, we have our weekends back."