Wayne was born in 1772 at Waynesborough, the family estate in Paoli, Pennsylvania, graduated from Dickinson College in Carlisle, Pennsylvania, then studied law and was admitted to the Chester County, Pennsylvania, bar in 1795. He was a member of the Pennsylvania House of Representatives from 1799 to 1801 and 1806, and served in the Pennsylvania State Senate in 1810. During the War of 1812, Wayne was captain of a troop of Pennsylvania Horse Cavalry, raised and equipped by himself, and was subsequently colonel of the Second Regiment, Pennsylvania Volunteer Infantry.
Wayne unsuccessfully ran as a Federalist candidate for Governor in 1814, but was elected to the Eighteenth Congress. He died in Chester County on October 25, 1852. He is buried in the family plot at St. David's (Radnor) Episcopal Church in Radnor, Pennsylvania.
- Anthony and Mary (Penrose) Wayne Family Bible http://genealogycenter.info/bibles/viewbiblepage_wayneanthony.php?p=10
- United States Congress. "Isaac Wayne (id: W000217)". Biographical Directory of the United States Congress.
- Pleasants, Henry; Delaware County Historical Society (1907). History of Old St. David's Church Radnor, Delaware County, Pennsylvania. John C.Winston Co. p. 206.
- The Political Graveyard
- Encyclopedia Dickinsonia
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James S. Mitchell
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