After study at the University of Leiden, The Netherlands, he became a professor at Kaieisho College in Tokyo. Together with Mori Arinori (1847–89), later minister of education, Nishi founded the famous Meirokusha publishing house. Its journal featured articles on a wide range of Western philosophers, including Jean-Jacques Rousseau, Montesquieu, Ernst Haeckel, John Stuart Mill, Herbert Spencer, and Henry Buckle. The publishing house also introduced other aspects of Western civilization to Japan.

Nishi not only translated J.S. Mill's Utilitarianism but also wrote many commentaries on Western philosophy. He is regarded as the first philosopher to create modern philosophical terminology in Japanese, which permitted Japanese philosophers to compare Oriental and Western thought.