His work represents a high point in the modern academic study of iconography, including his hugely influential[2] Renaissance and Renascences in Western Art and his masterpiece Early Netherlandish Painting.

He was immersed in an environment that valued education and cultural refinement from a young age and exposed to classical music and literature such as Divine Comedy, Shakespeare’s sonnets and the works of Johann Wolfgang von Goethe and Gotthold Ephraim Lessing.

He did not observe Jewish religious customs as an adult, but he remained proud of his heritage such as sharing story about his grandfather as a renowned Talmud scholar.

In the spring of 1917, he was considered fit for duty on the home front and was assigned a governmental position in Kassel, and later in Berlin, where he was responsible for distributing coal to the civilian.

Following Gustav Pauli's invitation on December 1919 to teach art history at the University of Hamburg, Panofsky agreed on the condition of simultaneously pursuing habilitation.

Pauli, reviewing the thesis by March 20, privately advised Panofsky to secure housing in Hamburg, anticipating a favorable outcome.

Though on July 3, 1920, based on letter to Dora Panofsky, his wife at that time revealed plans to revise the text suggesting the work was still in his possession.

Yet, by 1964, when Egon Verheyen inquired about the thesis after encountering its citation in Gert van der Osten’s article, Panofsky confirmed its loss, stating, “The original manuscript is lost”.

[17] In the Süddeutsche Zeitung, Willibald Sauerländer shed some light on the question of whether Heydenreich shared his recovery of the manuscript or not: "Panofsky has historically distanced himself from his early writings on Michelangelo, as he tired of the subject, and," according to Sauerländer "developed a professional conflict with Austro-Hungarian art historian Johannes Wilde, who accused Panofsky of not crediting him with ideas gleaned from a conversation they had about Michelangelo drawings.

First in a 1934 article, then in his Early Netherlandish Painting (1953), Panofsky was the first to interpret Jan van Eyck's Arnolfini Portrait (1934) as not only a depiction of a wedding ceremony, but also a visual contract testifying to the act of marriage.

In recent years, this conclusion has been challenged, but Panofsky's work with what he called "hidden" or "disguised" symbolism is still very much influential in the study and understanding of Northern Renaissance art.

His elder son, Hans A. Panofsky, was "an atmospheric scientist who taught at Pennsylvania State University for 30 years and who was credited with several advances in the study of meteorology".

Erwin Panofsky has been recognized as both a "highly distinguished" professor at the Institute for Advanced Study, Princeton, New Jersey, and in Jeffrey Chipps' biography of the subject as "the most influential art historian of the twentieth century".

"[29] The method of iconology, which had developed following Erwin Panofsky, has been critically discussed since the mid-1950s, in part also strongly (Otto Pächt, Svetlana Alpers).

[33] His work has greatly influenced the theory of taste developed by French sociologist Pierre Bourdieu, in books such as The Rules of Art and Distinction.