Sipser was born and raised in Brooklyn, New York and moved to Oswego, New York when he was 12 years old. He earned his BA in mathematics from Cornell University in 1974 and his PhD in engineering from the University of California at Berkeley in 1980 under the direction of Manuel Blum.
He joined MIT's Laboratory for Computer Science as a research associate in 1979 and became an MIT professor the following year. From 2004 until 2014, he served as head of the MIT Mathematics department. He was appointed Dean of the MIT School of Science in 2014. He is a fellow of the American Academy of Arts and Sciences. In 2015 he was elected as a fellow of the American Mathematical Society "for contributions to complexity theory and for leadership and service to the mathematical community."