ME, MYSELF & I features Moynihan in a comedy about the defining moments in one man's life over three distinct periods - as a 14-year-old in 1991, at age 40 in present day and at age 65 in 2042.
Saturday night's show will be hosted by Dwayne "The Rock" Johnson.
The veteran cast member's departure from the series comes as his new comedy pilot, Me, Myself & I, has been picked up to series by CBS, and will premiere on the network's fall schedule.
According to Deadline, which first reported the news, Moynihan signed a two-year extension after his original seven-year deal expired.
On the show Moynihan will play Alex Riley, a lifelong inventor who is trying to get a glimpse into the future but to do so, must overcome his inventors block by turning to his past. The actor pitched the show to advertisers during CBS' Upfronts presentation in NY on Wednesday before hurrying off for a run-through rehearsal at his "other show".
Beyond characters like the blubbering "Drunk Uncle", Moynihan regularly parodied Chris Christie during the 2016 presidential campaign until a certain someone became the official Republican nominee. John Larroquette stars as the older version of Moynihan's character.