In 1839, he graduated from the university and moved to the newly opened Pulkovo Observatory, where he was immediately appointed as assistant of the director (his father).

[5] During 1843 and 1844, Struve participated in longitude measurements between Altona, Greenwich and Pulkovo, which were based on large displacement of chronometers over the Earth surface.

The measurements extended through over 2,820 km, from Hammerfest in Norway to the Staraya Nekrasovka village by the Black Sea, and aimed to establish the exact size and shape of the Earth.

In 1861, in his report to the Academy of Sciences, he supported and developed the ideas of William Herschel that stars are formed from the diffuse matter.

[6][11] In 1872, he organized assistance with equipment to the newly opened observatory in Tashkent – a more southerly location offering clear skies for observations.

In 1874, he prepared several expeditions to monitor the transit of Venus across the solar disk in eastern Asia, Caucasus, Persia and Egypt.

Around 1845, von Struve's father withdrew from most management activities at the Pulkovo Observatory and focused on individual research.

[4][12] Struve remained a top authority at the Russian Academy and his instructions regarding staff appointments were generally followed without question.

The visit served several purposes, including ordering the Alvan Clark & Sons optics for the new 30-inch telescope in Pulkovo,[13] and it was a part of long-term Russia-US astronomy partnership during the 19th century.

By the initiative of Struve, two US astronomers, Simon Newcomb and Asaph Hall were appointed as Foreign Members of the Russian Academy of Sciences.

After retirement in 1889, Otto Wilhelm Struve stayed mostly in St. Petersburg, summarizing his observations and keeping correspondence with colleagues.

[4] Struve won the Gold Medal of the Royal Astronomical Society in 1850 for his work on "The Determination of the Constant of Precession with respect to the Proper Motion of the Solar System" published in 1840 .