A brief statement from LAFC said the club had decided to axe Dos Santos after less than a year in the job following "careful consideration."
"Marc has given a great deal to this club over the years, and we are grateful for his commitment, care and contributions to LAFC," President of Soccer Operations John Thorrington said in a statement.
"We wish Marc and his family all the best moving forward."
The statement said LAFC will name an interim coach soon ahead of a formal search for a permanent successor to Dos Santos, who joined the club as an assistant coach in 2022.
Dos Santos, 49, leaves LAFC with the club in sixth place in the Western Conference standings, with 41 points from 28 games.
The Canadian's dismissal came a day after LAFC were beaten 1-0 by FC Dallas on Saturday.