In 1965, Pupin was named a National Historic Landmark for its association with experiments relating to the splitting of the atom, achieved in connection with the later Manhattan Project.

[4][5][6] In 2009 the American Physical Society named Pupin Hall a historic site and honored Isidor Isaac Rabi for his work in the field of magnetic resonance.

The building's historic significance was secured with the first splitting of a uranium atom in the United States, which was achieved by Enrico Fermi in Pupin Hall on January 25, 1939, just 10 days after the world's first such successful experiment, carried out in Copenhagen, Denmark.

It is connected to the university tunnels, from which one can occasionally access the Manhattan Project's leftover cyclotron and other historic research facilities.

[8] The Center for Theoretical Physics, which opened in 2016, is on the ninth floor of Pupin and offers a modern office space covered in blackboards.

As Brian Greene put it, "the center space is designed to encourage interactions among faculty and students.”[9] The bust of Mihajlo Pupin is displayed near the main entrance.