The 31-year-old Mexican international's contract is expired and will not be renewed for the 2022 campaign.
"We thank Jonathan for his contributions to the LA Galaxy," said Galaxy president Chris Klein said in a team release. "In five seasons with the Galaxy, Jonathan was a key contributor and leader for us. We very much appreciate his work ethic, professionalism and passion during his time with our club and we wish him all the best."
Dos Santos contributed six goals and 12 assists in 103 matches (91 starts), becoming the 30th player in franchise history to appear in 100 regular-season games. He was an MLS All-Star in 2018 and 2019.
He scored one goal in 26 games (22 starts) in 2021 for the Galaxy (13-12-9, 48 points), who finished one spot out of playoff contention in the MLS Western Conference.
His departure opens up a Designated Player spot on the Galaxy roster.