It had a variety of responsibilities, including Irish policy, the Channel Islands, and foreign affairs concerning southern European powers such as France, Spain, Portugal, Switzerland, Italian states, Greece and the Ottoman Empire.

Domestic affairs in England and Wales were shared indifferently between the Southern and Northern Departments.

Scotland, which joined with England into the Kingdom of Great Britain after 1707, was at times represented by a separate Secretary of State for Scotland, though at others (1725–1741 and 1746–1782) it too was represented by the Northern and Southern Departments.

In 1782, the Northern and Southern Departments were reorganised, with the Foreign Office taking over their foreign affairs responsibilities and Home Office taking over their domestic, military affairs, and colonial responsibilities.

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