Struve, who was born at Kharkov in Russia, came from a long line of distinguished astronomers, being the great grandson of its founder Friedrich Georg von Struve. His father was the professor of astronomy and director of the observatory at the University of Kharkov and he had two uncles who were directors of German observatories. His studies at the university were interrupted by World War I but he finally graduated in 1919. Called up again in 1919 after the revolution, he ended up destitute in Turkey in 1920. Following a journey of some difficulty he finally arrived in America in 1921 where he attended the University of Chicago, obtaining his PhD in 1923. He worked at the Yerkes Observatory, serving as director from 1932 to 1947 as well as professor of astrophysics at Chicago for the same period. He played an important role in the founding of the McDonald Observatory on Mount Locke in Texas and the planning of its 82-inch (2.1-m) reflecting telescope, then the second largest in the world. He served as McDonald's first director from 1939 to 1950. Struve moved to a less demanding position at the University of California at Berkeley in 1950 but agreed in 1959 to become the first director of the National Radio Astronomy Observatory at Green Bank in West Virginia. Forced to resign in 1962 owing to ill health, he died shortly after.

Although Struve spent much of his time in administration and organization, he was able to conduct some major observational work. He made spectroscopic studies of binary and variable stars, stellar rotation, stellar atmospheres, and, possibly most important, of interstellar matter.

One of the problems facing astronomers at the beginning of the century was whether there was any interstellar matter and if so, did it significantly absorb or distort distant starlight. This was no trivial question for the answer could make nonsense of many accounts of the distribution of stars. In 1904 Johannes Hartmann had argued for the presence of interstellar calcium by pointing out that the calcium spectral lines associated with the binary system Delta Orionis did not oscillate with the other spectral lines as the stars orbited each other. This work was extended by Vesto Slipher in 1908 and 1912.

Struve produced evidence on the next crucial point as to whether the interstellar matter was diffuse and pervasive or only local and associated with individual star systems. In 1929, in collaboration with B. P. Gerasimovic, he showed that it exists throughout the Galaxy. This work was also done independently by John Plaskett. In 1937 Struve discovered the presence of interstellar hydrogen, in ionized form, which though much more prevalent than calcium was initially more difficult to detect.