Szybalski joined the Chemistry Department at the Lwów Polytechnic, where he was captivated by the lectures of Professor Adolf Joszt, a leading expert on processes of fermentation.

Szybalski survived the occupation by working as a feeder of lice in Rudolf Weigl's institute for typhus research.

Szybalski subsequently emigrated to the United States and became a professor of oncology at the McArdle Laboratory for Cancer Research, University of Wisconsin–Madison Medical School.

The research he conducted in the United States began with genetic studies of drug resistance that led to the use of multi-drug therapy that is nowadays widely used to treat bacterial and viral infections and cancer.

His studies of the antibiotic-producing soil microorganism, Streptomyces, yielded information that was useful in the commercial production of streptomycin, an effective therapeutic for treating tuberculosis.