Delamere was the eldest son of Thomas Cholmondeley, 1st Baron Delamere, and Henrietta Elizabeth Williams-Wynn, granddaughter of Prime Minister George Grenville. He was elected to Parliament for Denbighshire as a Tory in 1840, a seat he held until 1841, and then represented Montgomery from 1841 to 1847. In 1855 he succeeded his father as second Baron Delamere and entered the House of Lords.
Lord Delamere married, firstly, Lady Sarah Hay-Drummond, daughter of Thomas Hay-Drummond, 11th Earl of Kinnoull, in 1848. After his first wife's death in 1859 he married, secondly, Augusta Emily Seymour, daughter of Sir George Hamilton Seymour, in 1860. He died in August 1887, aged 75, and was succeeded in the barony by his son from his second marriage, Hugh Cholmondeley. Lady Delamere died in 1911.