He shared the 1999 Nobel Prize in Physics with his thesis advisor Martinus J. G. Veltman "for elucidating the quantum structure of electroweak interactions".

His contributions to physics include a proof that gauge theories are renormalizable, dimensional regularization and the holographic principle.

His great uncle was Nobel prize laureate Frits Zernike, and his grandmother was married to Pieter Nicolaas van Kampen, a professor of zoology at Leiden University.

His uncle Nico van Kampen was an (emeritus) professor of theoretical physics at Utrecht University, and his mother married a maritime engineer.

[2] After Gerard 't Hooft passed his high school exams in 1964, he enrolled in the physics program at Utrecht University.

Because he was so focused on science, his father insisted that he join the Utrechtsch Studenten Corps, a student association, in the hope that he would do something else besides studying.

In the course of his studies he decided he wanted to go into what he perceived as the heart of theoretical physics, elementary particles.

His uncle had grown to dislike the subject and in particular its practitioners, so when it became time to write his doctoraalscriptie (former name of the Dutch equivalent of a master's thesis) in 1968, 't Hooft turned to the newly appointed professor Martinus Veltman, who specialized in Yang–Mills theory, a relatively fringe subject at the time because it was thought that these could not be renormalized.

[3] In it he showed how to renormalize massless Yang–Mills fields, and was able to derive relations between amplitudes, which would be generalized by Andrei Slavnov and John C. Taylor, and become known as the Slavnov–Taylor identities.

Soon 't Hooft's second paper was ready to be published,[4] in which he showed that Yang–Mills theories with massive fields due to spontaneous symmetry breaking could be renormalized.

These two papers formed the basis of 't Hooft's dissertation, The Renormalization procedure for Yang–Mills Fields, and he obtained his PhD degree in 1972.

In this time he became interested in the possibility that the strong interaction could be described as a massless Yang–Mills theory, i.e. one of a type that he had just proved to be renormalizable and hence be susceptible to detailed calculation and comparison with experiment.

In 2007 't Hooft became editor-in-chief for Foundations of Physics, where he sought to distance the journal from the controversy of ECE theory.

't Hooft's research interest can be divided in three main directions: 'gauge theories in elementary particle physics', 'quantum gravity and black holes', and 'foundational aspects of quantum mechanics'.

His calculation showed that these contributions lead to an interaction between light quarks at low energies not present in the normal theory.

This work would be continued by Stanley Deser and another PhD student of Veltman, Peter van Nieuwenhuizen, who later found patterns in the renormalization counter terms, which led to the discovery of supergravity.

Together with Deser and Jackiw he published an article in 1984 describing the dynamics of flat space where the only local degrees of freedom were propagating point defects.

't Hooft refused to accept this problem, known as the black hole information paradox, and assumed that this must be the result of the semi-classical treatment of Hawking, and that it should not appear in a full theory of quantum gravity.