His Ph.D. thesis, written under the direction of Oscar Zariski, was on Valuation Ideals in Rings of Polynomials in Two Variables.

Seidenberg became an instructor in mathematics at the University of California, Berkeley, in 1945.

He published Prime ideals and integral dependence written jointly with Irvin Cohen, which greatly simplified the existing proofs of the going-up and going-down theorems of ideal theory.

In 1950, he published a paper called The hyperplane sections of normal varieties, which has proved fundamental in later advances.

At the time of his death, he was in the midst of series of lectures at the University of Milan.