Professor Nic Beech, who was appointed on October 31, is to become vice-chancellor of Middlesex University, which he said "represents a career ambition".
NHS Tayside vice-chairwoman Lorna Birse-Stewart will take over the post on a temporary basis, Health Secretary Jeane Freeman said.
Mrs Birse-Stewart was the interim chairwoman of the board before the arrival of Professor Beech, who is also leaving his role as vice-principal of the University of Dundee.
He will take up his new position at Middlesex University from February next year.
Prof Beech said: "It is with regret that I have to withdraw as chairman of Tayside but I have been offered a role which represents a career ambition.
"This does not in any way diminish my belief in the ambitious change programme in NHS Tayside and its leadership, and I was excited to be working with the team on a significant change and improvement project."
The Health Secretary said: "I wish Professor Beech well in his academic career. I have appointed Lorna Birse-Stewart, in her capacity as vice-chair, to take over the chair's responsibilities in providing the necessary leadership for the board."
She added: "Mrs Birse-Stewart brings a wealth of experience from her extensive work in the charitable sector and has been on the board for NHS Tayside since 2018.
"I am confident that Mrs Birse-Stewart will continue to ensure that the people of NHS Tayside have the best care experience possible."
The health board is one of four to have been escalated to the second highest stage of Government intervention, due to financial and leadership issues.