Tim Wolfe made the announcement as students and professors staged a walkout at the Columbia campus.
Some members of the university’s football team have threatened not to play at a game on November 7 over the racial issues.
Black student groups say racial slurs are commonly used around campus.
In his statement, Tim Wolfe said: “The frustration and anger that I see is clear and real and I don’t doubt it for a second.
“I take full responsibility for the frustration and inaction on this campus.”
Missouri graduate student Jonathan Butler, who had been participating in a hunger strike as a protest, said the resignation was a “great step towards change” but there was still a lot of work to do.
“We still have a lot of healing that needs to happen on campus,” Jonathan Butler said, adding that his hunger strike would now end.
Tim Wolfe served as president of the entire university system and not specifically for the flagship Columbia campus.
Concerned Student 1950, the student group that has been having a sit-in on campus since November 2, tweeted that Tim Wolfe’s resignation was a victory but its work was not done.
“Our brother can eat, but we are still owed Demands! Stay strong!” Concerned Student 1950 tweeted.
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