Nathaniel Middleton (1750–1807) was a civil servant of the British East India Company, closely involved with Warren Hastings and his dealings with the Nawab of Awadh during the 1770s, and later a principal witness at Hastings's trial.

The son of the Rev. Samuel Middleton (1703–1758), perpetual curate of Whitmore, Staffordshire, and his wife Mary, he was in British India as an East India Company writer by 1769. In 1773, with encouragement from his elder brother Samuel Middleton, Warren Hastings sent Nathaniel Middleton to the Awadh court at Lucknow, representing British interests with Shuja ud-Daula. This was the period of the First Rohilla War in which Awadh was allied to the British.

Shuja ud-Daula was properly the Nawab Wazir, since the wizarat of Delhi had been added to Awadh by his father, and is commonly known as the Wazir. Since the Battle of Buxar of 1764, in which Shuja ud-Daula and Awadh were on the losing side, Awadh had been falling into the orbit of British India, and had troops stationed for which it was required to pay. The Treaty of Benares of 1773 ratified the situation.

In 1774 Hastings was overruled in his policy by the Bengal Council and a combination of John Clavering, Philip Francis and George Monson. Middleton was replaced at Lucknow, where John Bristow took his place; but after Monson's death in 1776 Hastings reinstated him, the Wazir having in the meantime died and been replaced by his son Asaf-ud-Daula. Further changes occurred when Hastings in 1779 deferred to Eyre Coote's view that Middleton should be replaced by Charles Lambert Purling; but after a year Purling was recalled, and the responsibilities as Resident at Lucknow were divided between Bristow and Middleton, who was given financial duties. Bristow then had to step down in 1781.

Developments by 1782 caused Hastings to lose patience with the Wazir, who owed large sums of money. Middleton and a British force recovered funds directly, including from the Fyzabad palace. They used force, and distraint against the Wazir's mother Bahu Begam (the Begum), with threats to her staff. Hastings lost confidence in Middleton's proceedings with the Wazir, sending a negotiator and then removing Middleton by the autumn, to be replaced by Bristow.

Middleton, who had married in 1780, left the East India Company's service in 1784 and returned to England, having requested leave to depart on the Barwell from Hastings. John Charles Middleton who requested leave at the same time was Nathaniel's brother.

Francis, with polemical intent against Hastings, wrote of Middleton as "uncrowned king" of Awadh. He developed commercial interests there, including a saltpetre monopoly, and brought in British merchants. His business contacts included the Dutch East India Company, and he received a large related payment through the London counting-house Rumbold, Charlton & Raikes. One of the merchants who prospered under Middleton was John Pendred Scott, involved on a large scale in cotton goods at Tanda; he used Middleton's London account for clearing Dutch payments.

Bringing home an Indian fortune, Middleton became one of the reputed group of civilian nabobs in Great Britain, mentioned with Richard Barwell, Paul Benfield, Thomas Rumbold, and Sir Francis Sykes, 1st Baronet. He lived initially in Wimpole Street, London, and then in 1788 purchased the Townhill estate in what now is Southampton. He employed Thomas Leverton for building work there in 1792. The 1792 house was altered in the 1840s, and again by Leonard Rome Guthrie for Samuel Montagu, 1st Baron Swaythling around 1910. Montagu had bought the Townhill estate from Caleb William Gater, of the family of William Cator or Gater (see section on Family).