Lowth was born in Hampshire, England on November 27, 1710, the son of Dr William Lowth. He was educated at Winchester College and entered New College, Oxford in 1729 on a scholarship. Lowth obtained his BA in 1733 and his Master of Arts degree in 1737. In 1735, while still at Oxford, Lowth entered the Anglican Church and was appointed vicar of Overton, Hampshire, a position he retained until 1741, when he was appointed professor of poetry at Oxford.
In 1750 he was appointed archdeacon of Winchester. In 1752 he resigned the professorship at Oxford and married Mary Jackson. Shortly afterwards, in 1753, Lowth was appointed rector of East Woodhay. In 1754 he was awarded a Doctorate of Divinity by Oxford, for his treatise on Hebrew poetry entitled Praelectiones Academicae de Sacra Poesi Hebraeorum.
Lowth is no doubt best remembered for his publication in 1762 of A Short Introduction to English Grammar. Prompted by the absence of grammar textbooks in his day, Lowth set out to develop a system of grammar that elevated English to the level of Latin, and attempted to regulate English usage within the rules of Latin grammar. His most famous (or infamous) contribution to the study of grammar was his prescription that forbade the use of the split infinitive, a rule that has been a subject of dispute for grammarians ever since. Additionally, Lowth originated the antagonism towards sentences ending with a preposition, thus declaring a sentence such as "what did you ask for?" to be invalid. The textbook remained in standard usage throughout educational institutions until the early 20th century.
Lowth was appointed a fellow of the Royal Societies of London and Göttingen in 1765. He was consecrated bishop of St. Davids in 1766; however, before the end of the year he was transferred to the see of Oxford. He remained Bishop of Oxford until 1777 when he was appointed Bishop of London as well as dean of the chapel royal and privy councillor. In 1783 he was offered the chance to become Archbishop of Canterbury, but declined due to failing health.