William George Clark was born on 18 March 1821, the only son of Robert Clark (d. 1874), farmer, and his wife, Sarah (d. 1869), of Barford Hall, Yorkshire. He was educated at Sedbergh grammar school and at Shrewsbury School under B. H. Kennedy. He entered Trinity College, Cambridge, in 1840, and, after winning many prizes, was second in the classical tripos and second chancellor's medallist in 1844. He was a fellow of Trinity College from 1844 until his death, and was for several years tutor of his college; he was elected public orator of the university in 1857.
Clark travelled in the long vacations, and gathered materials for several publications, such as Gazpacho (1850) Peloponnesus, or, Notes of Study and Travel (1858) and Vacation Tourists (1861–1864), which includes Clark's impressions of Italy during Garibaldi's expedition of 1860, and of Poland during the insurrection of 1863. In 1850 Clark contributed to his old schoolmaster Kennedy's edition of the Sabrinae corolla. His constant facility and wit in classical composition were much admired. He published (anonymously) in 1849 a Score of Lyrics, and edited the first series of Cambridge Essays (1855), contributing a paper on classical education. He helped to establish and edit the Journal of Philology (from 1868), and also wrote for it; he also edited the essays of his friend George Brimley in 1858. Clark's principal and most enduring work was the Cambridge Shakespeare (1863–1866), mainly planned by him, with a complete collation of all the early editions, and a selection of emendations by later editors. Clark co-operated in the first volume with John Glover, and afterwards with W. Aldis Wright, successively librarians of Trinity. Their single-volume Globe edition of Shakespeare crystallized the editorial labours of a century (1864) and was for many years the standard edition worldwide.
Clark laboured for many years on an edition of Aristophanes, but was finally interrupted by declining health, and left little in a state for publication. He had been ordained in 1853, and published a few sermons, but in November 1869 he wrote to his bishop, stating that he wished to resign his orders, explaining his reasons fully in a pamphlet, called The Present Dangers of the Church of England. The Clerical Disabilities Act of 1870, which he joined in promoting, enabled him to abandon his clerical character. He had resigned the public oratorship in 1869, but continued to be vice-master of his college until 1872. A severe illness in the spring of 1871 broke down his health. Clark left Cambridge in the autumn of 1873; his powers gradually failed, and he died at the North-Eastern Hotel, York, on 6 November 1878. He was buried beside his parents at Gainsford, near his birthplace. He left property to Trinity College, from which an annual lectureship in English literature was founded and named after him; the first appointment was made in 1883.