He became a successful trader and entered local politics when he was elected in the city council as councillor on 19 October 1890.

King Leopold II appointed him mayor of Antwerp on 22 February 1909, much against the wishes of the Liberal Party, of which Jan De Vos was also member, who would have preferred the alderman (schepen) Victor Desguin.

De Vos negotiated terms with General Hans Hartwig von Beseler of the German Army in Kontich to the south of Antwerp.

De Vos signed the surrender of the city and the remaining fortresses around Antwerp on 10 October 1914.

After German capitulation, he was not prosecuted for collaboration and stayed on as mayor until 21 July 1921.