Phoebus Levene was born in Sagor in Russia. He grew up in St. Petersburg and studied medicine at the Imperial Military Medical Academy. As a student he worked in the laboratory of his organic chemistry professor where he likely developed an interest in biochemistry.

In 1891, because of growing anti-Semitism in Russia, Levene and his family emigrated to the U.S. They arrived on the symbolic day of July 4. Levene went back to Russia almost immediately to finish his medical degree, but by 1892, he was in New York and practicing medicine on the Lower East Side.

Levene did not give up research. He enrolled as a special student at Columbia University and he split his time between his medical practice and research in the department of physiology. By 1894, he began publishing papers on the chemical structure of sugars. Two years later, Levene received his first appointment as an Associate in the Pathological Institute of the New York State Hospitals. Unfortunately, around this time, Levene contracted tuberculosis and was forced to take time off to recuperate.

Levene used the time between 1896 and 1905 to regain his health and to work with a number of well-known chemists, including Albrecht Kossel and Emil Fischer, the nucleic acid and protein experts of the time. In 1905, Levene was hired by the newly established Rockefeller Institute of Medical Research to head the biochemical laboratory. Levene did most of his nucleic acid work at the Rockefeller and stayed there until his death.

Levene was a cultured man, an art lover and a collector. The walls of his house were lined with either prints and paintings or overflowing bookshelves. Levene was extremely well-read and was fluent in Russian, English, French and German. He also spoke passable Spanish and Italian. His experience, knowledge and his generosity made him a favorite with colleagues and friends. He was also said to be a great teacher, enthusiastic and supportive.

Although mostly remembered now for his incorrect tetranucleotide theory of DNA, Levene published over 700 original papers and articles on the chemical structures of many biochemicals. Levene died in 1940, before the true significance of DNA became clear.