Broadcaster NBC also said it would not be bringing back its weekly news magazine show "Rock Center" for the 2013-14 fall schedule, along with five other low-rated comedies.
The comedy "Go On," in which Perry played a sports radio host who joins a grief counseling group after the death of his wife, was one of a slew of low-rated NBC television shows that will not be renewed, the network said.
Perry, 43, has struggled to follow up his success as the hapless Chandler Bing in NBC's "Friends," which ended in 2004.
"Go On" received favorable reviews and attracted an audience of more than 16 million when it made its debut in August 2012. But audiences dropped off and the season finale in April was watched by less than 3 million people.
"Go On" followed the dark and short-lived 2011 series "Mr. Sunshine," in which Perry starred as well as co-created, and the 2006-07 "Studio 60 on the Sunset Strip" that was canceled after one season.
Perry's "Friends" co-star Jennifer Aniston has launched a second career as a romantic comedy movie actress, while Lisa Kudrow and Courteney Cox have made several movies and TV shows, David Schwimmer has appeared on stage and tried his hand at directing, and Matt LeBlanc won a Golden Globe in 2012 for playing a version of his skirt-chasing "Friends" bachelor character Joey in the Showtime and BBC comedy "Episodes."
NBC, which has struggled to replace 1990s' hits like "Friends," "Cheers," "Frasier," and "Will & Grace," has also axed White House-based comedy "1600 Penn," the Jimmy Fallon-created comedy "Guys With Kids," "Whitney" and "Up All Night."
"Rock Center," hosted by veteran NBC News journalist Brian Williams, made its debut in October 2011 in what the network hoped would be a fast-paced but serious approach to news. But it struggled to find an audience and viewership has fallen in recent weeks to around 4 million after NBC switched the hourlong show to several different time slots.