In 1852 Monsell was appointed Clerk of the Ordnance by Lord Aberdeen, a post he retained until 1857, the last two years under the premiership of Lord Palmerston. In 1855 he was sworn of the Privy Council. He was briefly President of the Board of Health under Palmerston in 1857 and later served under Lord Russell as Paymaster-General and Vice-President of the Board of Trade in 1866 and under William Ewart Gladstone as Under-Secretary of State for the Colonies between 1868 and 1871 and as Postmaster-General between January 1871 and November 1873. He was also Lord Lieutenant of County Limerick between 1871 and 1894 and Vice-Chancellor of the Royal University of Ireland between 1885 and 1894.