[1][2] Mazzucato earned a master's degree in physics in 1994 from the University of Milan, with a thesis on topological quantum field theory under the supervision of Paolo Cotta-Ramusino.

[3] She went to the University of North Carolina at Chapel Hill for doctoral study, initially planning to work in quantum cohomology,[3] but switched to functional analysis with Michael E. Taylor as her doctoral advisor.

[5] Mazzucato was the winner of the Ruth I. Michler Memorial Prize of the Association for Women in Mathematics for 2011–2012, which she used to fund a research visit to Cornell University.

[2] At Cornell, she gave the Michler Lecture on "The Analysis of Incompressible Fluids at High Reynolds Numbers".

[6] She was named a SIAM Fellow in the 2021 class of fellows, "for discerning analysis of fundamental problems in partial differential equations and mathematical fluid mechanics including boundary layers, transport, and mixing".