In April 1783, Portland was brought forward as titular head of a coalition government whose real leaders were Charles James Fox and Lord North. He served as First Lord of the Treasury in this ministry until its fall in December of the same year.
In 1789, Portland became one of several vice presidents of London's Foundling Hospital. This charity had become one of the most fashionable of the time, with several notables serving on its board. At its creation, fifty years earlier, Portland's father, William Bentinck, 2nd Duke of Portland, had been one of the founding governors, listed on the charity's royal charter granted by George II. The hospital's mission was to care for the abandoned children in London and it achieved rapid fame through its poignant mission, its art collection donated from supporting artists and popular benefit concerts put on by George Frideric Handel. In 1793, Portland took over the presidency of the charity from the Right Honourable Lord North.
Along with many other conservative Whigs (such as Edmund Burke), Portland was deeply uncomfortable with the French Revolution, and ultimately broke with Fox over this issue, joining Pitt's government as Home Secretary in 1794. He continued to serve in the cabinet until Pitt's death in 1806 - from 1801 to 1805 as Lord President of the Council, and then as a Minister without Portfolio.
When Pitt's supporters returned to power after the collapse of the Ministry of all the Talents in March, 1807, Portland was, once again, an acceptable figurehead for a fractious group of ministers who included George Canning, Lord Castlereagh, Lord Hawkesbury, and Spencer Perceval.
Portland's second government saw the United Kingdom's complete isolation on the continent, but also the beginning of recovery, with the start of the Peninsular War. In late 1809, with Portland's health poor and the ministry rocked by the scandalous duel between Canning and Castlereagh, Portland resigned, dying shortly thereafter.
He was Recorder of Nottingham until his death in 1809.
The department of Manuscripts and Special Collections, The University of Nottingham holds a number of papers relating to the 3rd Duke: the 3rd Duke's personal and political papers (Pw F) are part of the Portland (Welbeck) Collection; and the Portland (London) Collection (Pl) contains correspondence and official papers of the 3rd Duke, especially in series Pl C.
The Portland Estate Papers held at Nottinghamshire Archives also contain items relating to the 3rd Duke's properties.