During the Second Anglo-Dutch War, Clifford served as one of four Commissioners for taking Care of Sick and Wounded Seamen and for the Care and Treatment of Prisoners of War (the others were Sir William D'Oyly, John Evelyn and Bullen Reymes).

[2] In August 1665, Clifford was named Ambassador Extraordinary to Sweden; he traveled to Denmark in October, before returning to Britain the following February.

At the end of the Dutch war in 1669 he intrigued against the peace treaty, preferring the French interests.

King Charles II entrusted for safekeeping to Clifford, his favorite aide, the British state papers of the 1670 Treaty of Dover, which "led to war between England and the Netherlands and might have ended British parliamentary rule and the Church of England".

He was Lord High Treasurer from 28 November 1672 to June 1673, when, as a Roman Catholic, he found himself unable to comply with the Test Act and resigned.