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Forced out of his university faculty position in at the University of St. Petersburg due to his Christian faith, he emigrated to Czechoslovakia at the invitation of Tomáš Masaryk, and as a professor at the Russian University of Prague in Bratislava became part of a vibrant network of ex-Marxist Russian Orthodox emigré intellectuals in Europe between the wars. After World War II he joined the faculty of St. [[St. Vladimir's Orthodox Theological Seminary (Crestwood, New York)|Vladimir's Seminary]], then in New York City, in America, and later moved to Paris where he died.

Prof. Lossky's legacy includes the work of his son Vladimir Lossky, a prominent modern Orthodox theological writer, whose background in philosophy and Orthodoxy he helped to shape. His most famous university student, while he was still teaching in St. Petersburg after the Revolution, was the writer and atheist-libertarian philosopher Ayn Rand, who also became an emigré settling in America. She later appreciatively recalled the elder Lossky as the only one of her university professors in the newly communist Russia whom she remembered, for the influence of his teaching on of classical philosophy on her work, but criticized what she considered to be his otherworldly Christian mysticism. (Despite the connection with whatever effect his lectures had on an undergraduate Rand, and the classification of Lossky's his philosophy as reflecting in part a metaphysical libertarianism, his later political views after his rejection of Marxism and atheism have nonetheless been described as Fabian Socialist.)