The Secretary of State for the Southern Department was a position in the cabinet of the government of United Kingdom up to 1782.

Before 1782, the responsibilities of the two British Secretaries of State were divided not based on the principles of modern ministerial divisions, but geographically. The Secretary of State for the Southern Department, the more senior Secretary of State, was responsible for Southern England, Wales, Ireland, the American colonies (until 1768), and relations with the Roman Catholic and Muslim states of Europe. The more junior Secretary of State for the Northern Department was responsible for Northern England, Scotland, and relations with the Protestant states of Northern Europe.

Secretaries of State for the Southern Department, 1660-1782

• Sir Edward Nicholas: 1 June 1660 - 20 October 1662
• Henry Bennet, 1st Earl of Arlington: 20 October 1662 - 11 September 1674
• Henry Coventry : 11 September 1674 - 26 April 1680
• Robert Spencer, 2nd Earl of Sunderland: 26 April 1680 - 2 February 1681
• Sir Leoline Jenkins: 2 February 1681 - 14 April 1684
• Robert Spencer, 2nd Earl of Sunderland: 14 April 1684 - 28 October 1688
• Charles Middleton, 2nd Earl of Middleton: 28 October - 2 December 1688
• Charles Talbot, 12th Earl of Shrewsbury: 14 February 1689 - 2 June 1690
• Daniel Finch, 2nd Earl of Nottingham: 2 June 1690 - November 1693
• Sir John Trenchard: November 1693 - 27 April 1695
• Charles Talbot, Duke of Shrewsbury: 27 April 1695 - 12 December 1698
• James Vernon : 12 December 1698 - 14 May 1699
• Edward Villiers, 1st Earl of Jersey: 14 May 1699 - 27 June 1700
• James Vernon : 27 June 1700 - 4 January 1702
• Charles Montagu, 4th Earl of Manchester 4 January - 1 May 1702
• Daniel Finch, 2nd Earl of Nottingham: 2 May 1702 - 22 April 1704
• Sir Charles Hedges : 18 May 1704 - 3 December 1706
• Charles Spencer, 3rd Earl of Sunderland: 3 December 1706 - 13 June 1710
• William Legge, 1st Earl of Dartmouth: 15 June 1710 - 6 August 1713
• Henry St John, 1st Viscount Bolingbroke: 17 August 1713 - 31 August 1714
• James Stanhope: 27 September 1714 - 22 June 1716
• Paul Methuen : 22 June 1716 - 10 April 1717
• Joseph Addison: 12 April 1717 - 14 March 1718
• James Craggs the Younger: 16 March 1718 - 16 February 1721
• John Carteret, 3rd Lord Carteret: 4 March 1721 - 31 March 1724
• Thomas Pelham-Holles, 1st Duke of Newcastle: 6 April 1724 - 10 February 1746
• John Carteret, 3rd Lord Carteret: 10 February - 14 February 1746
• Thomas Pelham-Holles, 1st Duke of Newcastle: 14 February 1746 - 12 February 1748
• John Russell, 4th Duke of Bedford: 12 February 1748 - 13 June 1751
• Robert Darcy, 4th Earl of Holdernesse: 18 June 1751 - 23 March 1754
• Sir Thomas Robinson: 23 March 1754 - October 1755
• Henry Fox: 14 November 1755 - 13 November 1756
• William Pitt the Elder: 4 December 1756 - 6 April 1757
• Robert Darcy, 4th Earl of Holdernesse: 6 April - 27 June 1757
• William Pitt the Elder: 27 June 1757 - 5 October 1761
• Charles Wyndham, 2nd Earl of Egremont: 9 October 1761 - 21 August 1763
• George Montague-Dunk, 2nd Earl of Halifax: 9 September 1763 - 10 July 1765
• Henry Seymour Conway: 12 July 1765 - 23 May 1766
• Charles Lennox, 3rd Duke of Richmond and Lennox: 23 May - 29 July 1766
• William Petty, 2nd Earl of Shelburne: 30 July 1766 - 20 October 1768
• Thomas Thynne, 3rd Viscount Weymouth: 21 October 1768 - 12 December 1770
• William Henry Nassau de Zuylestein, 4th Earl of Rochford: 19 December 1770 - 9 November 1775
• Thomas Thynne, 3rd Viscount Weymouth: 9 November 1775 - 24 November 1779
• Wills Hill, 1st Earl of Hillsborough: 24 November 1779 - 27 March 1782