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Lowther was born at Whitehaven, St Bees, Cumberland, the son of Sir Christopher Lowther, 1st Baronet, and his wife, Frances Lancaster, daughter of Christopher Lancaster of Stockbridge, Westmoreland. He was educated at Ilkley, Yorkshire and Balliol College, Oxford (matriculated 1657) 
Lowther owned large coal estates near Whitehaven, and worked to develop the mines and the port. He oversaw the growth of Whitehaven from a small fishing village to a planned town for the colliery workers. He served as Member of Parliament for Cumberland from 1665 to 1701, and a Lord Commissioner of the Admiralty from 1689 to 1696.
Lowther died at Whitehaven and was buried at St Bees.
Lowther married Jane Leigh, daughter of Woolley and Elizabeth Leigh of Addington, Surrey and had three children:
- Sir Christopher Lowther, 3rd Baronet (c.1666–1731)
- Jane Lowther (1667 – 27 February 1730), unmarried
- Sir James Lowther, 4th Baronet (1673–1755)
He disinherited his elder son, Christopher, as a spendthrift, and left his estates to his younger son, James.
- D.R. Hainsworth ed. (1983). The Correspondence of Sir John Lowther of Whitehaven 1693-1698. A provincial community in wartime. London: The British Academy. ISBN 0-19-726016-0.
- History of Parliament Online - Lowther, Sir John
- Beckett, J.V. (1980). "The Disinheritance of Sir Christopher Lowther in 1701". Transactions of the Cumberland and Westmorland Antiquarian and Archaeological Society. 80: 131–136.
- Beckett, J. V. (2004). "Lowther, Sir James, fourth baronet (bap. 1673, d. 1755)". Oxford Dictionary of National Biography. Oxford University Press. Retrieved 21 December 2006.
|Parliament of England|
Sir Patricius Curwen, Bt
Sir George Fletcher, 2nd Baronet
|Member of Parliament for Cumberland
With: Sir George Fletcher, Bt 1665–1679, 1681–1685, 1689–1701
Richard Lamplugh 1679
Viscount Morpeth 1679–1681
The Viscount Preston 1685–1689
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