He was educated at the Lazarist missionary school in Damascus and later at the military academy in Istanbul.
He was active in the Ottoman government, and later served as the first prime minister in republican Syria. He began his career as a government clerk, and was soon promoted to the prestigious position of inspector-general of the Ministry of Awqaf. He was laid off when the Committee of Union and Progress (CUP) seized control of the ministry in 1911.
After his defeat in the 1912 parliamentary elections, he moved to Cairo, and helped found the opposition party, Ottoman Party for Administrative Decentralization. The CUP interpreted diplomatic correspondence between the party and French and British agents as a proof that the party was aiming to guarantee the cession of the Arabic-speaking provinces from the Ottoman Empire. In 1913, al-Azm and other figures in the party were sentenced to death in absentia and they lived as exiles in Cairo.
He opposed the Arab Revolt and called it the "Hijazi revolt". He allied himself with the French mandate authorities, and was appointed the first governor of the State of Damascus in 1921. In 1921 he narrowly escaped an assassination attempt while on visit to Quneitra with the French High Commissioner Henri Gouraud.
In 1932, following the election of Muhammad Ali al-Abid, he was invited to form a cabinet, but the nationalist leaders boycotted the parliament. His rule between 1932-1934 was met with large opposition from the National Bloc.