Nier showed an early ability in mathematics and science, coupled with an aptitude for craft and mechanical work.

Nier's German immigrant parents had little education or financial resources but their determination for his development meant that he was able to attend the nearby University of Minnesota.

In 1940, on the request of Enrico Fermi, he and a few students, including Edward Ney, prepared a pure sample of uranium-235 using an early mass spectrograph designed by Nier,[5][6] for John R. Dunning's team at Columbia University.

On the day of its receipt (it was sent by US Postal Mail), Dunning's team was able to demonstrate that uranium-235 was the isotope responsible for nuclear fission, rather than the more abundant uranium-238.

[8] The Martian crater Nier [11] and the mineral nierite (tiny silicon nitride inclusions in meteorites)[12] were named after him.