Vieira, 57, left the program so she could spend more time with her family, including her journalist husband Richard Cohen, who has multiple sclerosis.
Cohen was by Vieira's side, along with "Today" stars Matt Lauer, Al Roker and Ann Curry, as Vieira left the studio for the last time after watching taped tributes from celebrities and highlights from her tenure on the show, People.com said.
"I have never enjoyed working with anyone as I have enjoyed working with Meredith," said Lauer.
People.com said he went on to describe the experience as "a privilege" and "a great ride."
"It started to hit me that this was the last day and I tried to push it back -- way back -- somewhere in the back of my head," Vieira told "Access Hollywood" Wednesday in an interview on the set of "Today."
"When I got here, I had to face the facts, even though this is my choice. It's really hard to leave this place."