He succeeded his grandfather Griffith Rice, MP in 1728, his father having previously died in 1727, inheriting Newton House and the Dynefwr Estate near Llandeilo, Carmarthenshire.

[1] At the general election of 1754 he was returned for Carmarthenshire after a warm contest with Sir Thomas Stepney, 7th Baronet, and retained his seat, over a period of twenty-five years, until his death, being re-elected four times without opposition.

By his marriage, on 16 August 1756, with Cecil (1733–1793), daughter of William Talbot, 2nd Baron Talbot of Hensol, Lord Steward, he increased his political influence, and on 21 March 1761 he accepted office under the Duke of Newcastle as a Lord Commissioner of the board of trade and foreign plantations, with a salary of £1,000 a year.

This post he held in successive ministries until April 1770, when Lord North selected him for the court appointment of Treasurer of the Chamber, and he was sworn a member of the Privy Council on 4 May following.

In the late 1700s, George Rice and his wife Cecil began the construction of a landscape garden at Newton House, hiring eminent architect Capability Brown in 1775 to assume responsibility for the development.