Sir John was the son of Dr John Joseph Esmonde MP (1862–1915), of Drominagh, Borrisokane, County Tipperary. On the death of his father in 1915, he was elected in his place (opposed by two nationalist contenders) as Irish Parliamentary Party MP for North Tipperary while serving in World War I with the Leinster Regiment, then as Captain The Royal Dublin Fusiliers with the Intelligence Corps; he was an engineer.
He was one of five Irish MPs who served with Irish regiments in World War I, the others Stephen Gwynn, Willie Redmond, William Redmond and D. D. Sheehan as well as former MP Tom Kettle. John Lymbrick Esmonde served with the forces that put down the Easter Rising. He withdrew without defending his seat in the 1918 general election. He inherited the Esmonde Baronetcy when the senior male line died out in 1943.
He subsequently served as a Fine Gael Teachta Dála (TD) for Wexford, where he won a seat at the 1937 general election. He was re-elected in 1938 and 1943, but lost his Dáil seat in the 1944 election. He became a barrister at the King's Inns, Dublin, called to the inner Bar as Senior Counsel in 1942, Bencher 1948. He was re-elected TD for Wexford in the 1948 general election serving until the 1951 general election, when he retired from politics. In 1948 he was suggested as possible Taoiseach by Seán MacBride, on the grounds that he had no link to either side in the Civil War.
His younger brother Lt. Geoffrey Esmonde (1897–1916) aged 19 was killed in action in World War I serving with the 4th Tyneside Irish Battalion of the Northumberland Fusiliers. His second younger brother was Sir Anthony Esmonde, 15th Baronet (1899–1981). His half-brother Eugene Esmonde was awarded a VC posthumously for in February 1942 leading the air attack on the German battleships Scharnhorst & Gneisenau as they made a dash through the English Channel.