Lyttelton unsuccessfully contested Worcestershire in March 1806, but was returned in the following year, and represented the county until 1820 for the Whig party. His maiden speech was made on 27 February 1807 in favour of the rejection of the Westminster petition; and on 16 March he brought forward a motion expressing regret at the substitution of the Duke of Portland's administration for Lord Grenville's. He attacked the new ministers, especially Spencer Perceval, for bigotry. He supported the naval expedition to Copenhagen in opposition to the bulk of his party, but voted with them on the motion of Samuel Whitbread for the production of papers relative to it. . Lyttelton alleged that the Duke, who was the second child of George III, had corrupted members of parliament. Lyttelton felt the Whig jealousy of the influence of the court. In supporting John Christian Curwen's bill for the prevention of the sale of seats, he suggested that the Duke of York and Albany, the late Commander-in-Chief of the Forces, had to some extent corrupted members of parliament; and in speaking on the budget resolutions of 1808 he declared his belief that the influence of the prerogative had increased. Again, on 4 May 1812, in a debate on the Royal Sinecure Offices Bill, he said that the Prince Regent was surrounded by favourites. Nevertheless, Lyttelton in 1819 thought that the "revolutionary faction of the radicals" ought to be opposed. In the same session he thought an inquiry was needed into the Peterloo massacre. Lyttelton advocated abolishing the system of having climbing boys sweep chimneys, and was a strong opponent of the property tax. He supported Richard Brinsley Sheridan's motion of 6 February 1810 against the standing order for the exclusion of strangers from the house. In the same session, on 16 February, he opposed the voting of an annuity to the Duke of Wellington. He spoke strongly against the Alien Bill in 1816 and 1818.
's Letters of Peter Plymley were for a time ascribed to Lyttelton before their authorship was known. In August 1815, through his friendship with the captain, he obtained a passage on board from Portsmouth to Plymouth to witness Napoleon's departure into exile, and privately printed 52 copies of An Account of Napoleon Buonaparte's Coming on Board H.M.S. Northumberland, 7 Aug. 1815; with Notes of Two Conversations Held with Him. He also printed a Catalogue of Pictures at Hagley, and published Private Devotions for School Boys.
George William Lyttelton, 4th Baron Lyttelton he married Mary Glynne on 25 July 1839. They have twelve children. He remarried Sybella Harriet Clive on 10 June 1869. They have three daughters
The Honorable Spencer Lyttelton he married Henrietta Cornewall on 10 August 1848. They have one son.
Reverend The Honorable William Lyttelton he married Emily Pepys on 28 September 1854. He remarried Constance Yorke on 5 February 1880.
The Honorable Lavinia Lyttelton she married Reverend Henry Glynne rector of Hawarden. on 14 October 1843. They have four children.