Ryan, 43, is exiting the Fox crime drama to focus on other projects, according to The Hollywood Reporter, who first reported the news. The creator of The Shield is currently working on Terriers, a new FX comedy about a ex cop-turned-private eye, and Fox's Ridealong, a police procedural set in Chicago.
Ryan joined Lie to Me as the series' new showrunner at the beginning of its sophomore season. The drama, starring Tim Roth, attracted just 6.63 million viewers for its last new episode in December.
Lie to Me's remaining 12 episodes will air on Fox beginning on June 7.
A show rep could not immediately be reached for comment.