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Grenville was the eldest son of the 1st Duke of Buckingham and Chandos, and was born at the family seat of Stowe in Buckinghamshire. He was styled Lord Cobham until 1813, Earl Temple from 1813 to 1822, and then Marquess of Chandos.
Following his education at Eton College and Oriel College, Oxford, and a spell on the Grand Tour during which he fathered an illegitimate child, he entered parliament as one of the M.P.s for Buckinghamshire in 1818.
Chandos was a strong opponent of Catholic emancipation in the 1820s, and an advocate of parliamentary reform. The 'Chandos clause' in the 1832 Reform Act was his work. His support of the Corn Laws and the agricultural interest gained him much support among farmers. Having succeeded his father as 2nd Duke in 1839, he resigned as Lord Privy Seal over the issue of the Corn Laws in 1842. He henceforth took little further part in active politics.
The financial difficulties his father had left with him, combined with his own extravagance, led him in 1848 to the drastic and humiliating measure of auctioning the contents of Stowe, and selling the majority of his land. He was forced to concede control of the estate to his son. Following his continued infidelities, the Duchess of Buckingham obtained a legal separation from him in 1850.