In a ministerial career spanning nearly half a century, he notably served as Home Secretary and Chancellor of the Exchequer and was three times Lord President of the Council.

In February 1806 he became Chancellor of the Exchequer in Lord Grenville's Ministry of All the Talents, being at this time member for the University of Cambridge, but he lost both his seat and his office in 1807.

In 1809 he became Marquess of Lansdowne, and in the House of Lords and in society he continued to play an active part as one of the Whig leaders.

His chief interest was perhaps in the question of Roman Catholic emancipation, a cause which he consistently championed, but he sympathised also with the advocates of the abolition of the slave trade and with the cause of popular education.

Lansdowne, who had succeeded his cousin, Francis Thomas Fitzmaurice, as 4th Earl of Kerry in 1818, took office with George Canning in May 1827 and was Secretary of State for the Home Department from July of that year until January 1828.