Born in the village of Shemokmedi (Guria, Georgia),[1] Makharadze studied at the Theological Seminary in Tbilisi and later graduated from the Veterinary Institute of Warsaw (Poland).

In 1903, he joined the Caucasian Joint Committee of the Russian Social Democratic Labour Party and played an active role in the 1905 Revolution in the Caucasus; he was allegedly involved in the assassination of the prominent Georgian public figure Ilia Chavchavadze in 1907.

In 1907–1915, he led various Bolshevik groups in Transcaucasia and, after the February Revolution, he co-founded the Tbilisi Soviet of Workers' Deputies.

In April 1917, he was elected as a delegate to the 7th RSDRP(B) Conference and served in the Bolshevik Caucasian Region Committee.

In 1922, Makharadze was involved in the Georgian Affair alongside Polikarp Mdivani and others; their group opposed Sergo Ordzhonikidze's designs with respect to Georgia.