Born in 1878 in the Yekaterinoslav Governorate of Ukraine in the Russian Empire to a Jewish family (of possibly Sephardic lineage) he said at his trial near the end of his life that "my father was a Hebrew teacher.

Having left school at 11, he returned to complete his education at the age of 20, served two years in the army (1901–1903), and joined the Russian Social Democratic Labour Party (RSDLP) in Yekaterinoslav in 1901.

He spent the period from 1908 to 1917 in Paris, where at different times he ran an employment bureau for Russian émigrés, an adult school for electricians, a bakers' co-operative, and a garage.

Even after rejoining the party, Lozovsky retained an independent position as secretary of the central trade union council, and on 17 November 1917, ten days after the Bolshevik revolution, published a personal credo, a series of statements each beginning "I cannot, in the name of party discipline stay silent..." Each statement was a protest against an aspect of the embryonic dictatorship - official lawlessness, arbitrary arrests, conscription, one-party rule etc.

He wanted the Bolsheviks to form a coalition with other socialist parties, and protested at the dissolution of the Russian Constituent Assembly and, later, against the decision to sign a peace treaty with Germany.

Victor Serge remembered him as having "the air of a slightly fastidious schoolmaster amidst his world-wide assortment of trade union militants whose political horizons did not extend very far beyond their own working-class districts at home".

[6] The Profintern was wound up in 1937, when the communist policy changed to advocating a united front against fascism, and Lozovsky was appointed Deputy People's Commissar for Foreign Affairs, tasked with handling the Far East and Scandinavia.

In this capacity, he became a familiar figure to Western correspondents based in Moscow, one of whom wrote that "with a smooth, cosmopolitan veneer...and with his barbiche and carefully cut clothes, (he) looked rather like an old boulevardier, whom one could well imagine on the terrace of the Napolitain during la belle epoque".

After the proclamation of the state of Israel (14 May 1948), Stalin interpreted this talk as a Jewish conspiracy, and ordered the police to organise a show trial, with Lozovsky as the main defendant.

Following the release of the documents, it also emerged that Nikita Khrushchev issued a posthumous pardon to Lozovsky and to all executed members of the Jewish Anti-Fascist committee,[12] stating that the trials were conducted in "flagrant violations of the law".