He is best remembered for having written along with Warren Sturgis McCulloch, a seminal paper in scientific history, titled A Logical Calculus of Ideas Immanent in Nervous Activity (1943).

Prior to that paper, he formalized his ideas regarding the fundamental steps to building a Turing machine in "The Bulletin of Mathematical Biophysics" in an essay titled "Some observations on the simple neuron circuit".

He is widely remembered for having spent three days in a library, at the age of 12, reading Principia Mathematica and sent a letter to Bertrand Russell pointing out what he considered serious problems with the first half of the first volume.

[3] Russell was a visiting professor at the University of Chicago in the fall of 1938, and he directed Pitts to study with the logician Rudolf Carnap.

[7][8][9] During his studies under Carnap, Pitts was also a regular attendant at Nicolas Rashevsky’s seminars in theoretical biology, which included Frank Offner, Herbert Landahl, Alston Householder, and the neuroanatomist Gerhardt von Bonin from the University of Illinois at Chicago.

In 1941 Warren McCulloch took a position as professor of psychiatry at the University of Illinois at Chicago, and in early 1942 he invited Pitts, who was still homeless, together with Lettvin to live with his family.

After five years of unofficial studies, the University of Chicago awarded Pitts an Associate of Arts (his only earned degree) for his work on the paper.

[13] From 1946, Pitts was a core member of the Macy conferences, whose principal purpose was to set the foundations for a general science of the workings of the human mind.

In 1959, the paradigmatic "What the Frog’s Eye Tells the Frog’s Brain" (credited to Humberto Maturana, Lettvin, McCulloch and Pitts) conclusively demonstrated that "analog processes in the eye were doing at least part of the interpretive work" in image processing as opposed to "the brain computing information digital neuron by digital neuron using the exacting implement of mathematical logic", leading Pitts to burn his unpublished doctoral dissertation on probabilistic three-dimensional neural networks and years of unpublished research.