The Terriers have parted company with Clark and his coaching staff, despite the club being in fourth place in the league.
“This was a very difficult decision; one not taken lightly or in response to one result. Concerns have been raised over recent weeks,” said chairman Dean Hoyle.
“Lee and his coaching staff have put their all into the job over the past three seasons and he has made a huge contribution to the club.
“However with 16 matches to go we still have an opportunity to achieve promotion and we have made this change with this in mind.”
Huddersfield academy manager Mark Lillis will take temporary charge of the first team.