The remake of the hit British sitcom debuted to around 1m viewers on the channel over the summer, but its ratings had fallen to nearly 600,000 for its final season one episode and will now not be picked up for a second run, reports Deadline.
"While we won't be moving forward with another season of The Inbetweeners, we enjoyed working with the show's creators and such a talented, funny cast," an MTV spokesperson said.
The news comes after MTV head of programming David Janollari was replaced by Susanne Daniels earlier this month.
The comedy starred Joey Pollari, Bubba Lewis, Zack Pearlman and Mark L Young as four high school students struggling in their quest to be cool and get girls, with Arrested Development's Brad Copeland serving as showrunner.
British Inbetweeners star Blake Harrison and co-creator Iain Morris both stood up for the remake before its premiere, following a hostile reaction from some fans of the original.
Morris wrote: "Brad, the showrunner, is a very funny man who has worked on Arrested Development and My Name Is Earl, two shows I love.
"[Co-creator] Damon [Beesley] and I didn't have a lot to do with it because we wanted it to be different and American, and it is, I think in a positive way."
The original Channel 4 show starring Harrison, Joe Thomas, Simon Bird and James Buckley ran for three series and a movie between 2008 and 2011.
Morris recently revealed that work is progressing on a sequel to The Inbetweeners Movie, following the huge success of the first film.
"The last thing any of us wants is a cheap cash-in," he explained.
"At the moment the script is at version 0.5, so we're getting close... but we're not there yet."
Watch Simon Bird discuss the sequel possibilities for The Inbetweeners Movie with Digital Spy below: