Wyse was born in the Manor of St. John, Co. Waterford on 9 December 1791. He was educated at Stonyhurst College, Lancashire, TCD, and Lincoln's Inn, London. He spent two years in Italy, between 1814 and 1816, and a further two years visiting Athens, Istanbul, Egypt, and the Middle East. In March 1821 he married Laetitia Bonaparte who was the eldest daughter of Lucien Bonaparte. They lived in Viterbo. They had two sons. However the marriage broke down. Laetitia left him in 1828 and they never met again.

Wyse returned to Ireland in 1825 and entered politics. He took part in the Catholic Emancipation struggle and became MP for Tipperary in 1830. He was MP for Waterford between 1835 and 1847. He was particularly interested in education and introduced many reforms. Wyse wrote a number of books including:- Walks in Rome, Oriental Sketches, and other works. Wyse was appointed British diplomat in Athens in 1849. He died there on 16 April 1862.