Barrett was born in Essex, the son of a farmer. He made his first appearance on the stage at Halifax in 1864, and then played in the provinces alone and with his wife, Caroline Heath, in East Lynne. After managerial experiences at Leeds and elsewhere, in 1879 he took the management of the old Court theatre, where he introduced Madame Modjeska to London, in an adaptation of Maria Stuart (by Schiller), Adrienne Lecouvreur, La Dame aux camélias and other plays. It was not till 1881, however, when he took the Princess's theatre, that he became well-known to the public in the emotional drama, The Lights o' London, by G. R. Sims.
The play which made him an established favourite was Henry Arthur Jones' The Silver King, perhaps the most successful melodrama of the century, produced in 1882 with himself as Wilfred Denver, his brother George (an excellent comedian) in the cast, and E. S. Willard as the "Spider," – this being the part in which Willard, afterwards a well-known actor both in America and England, first came to the front. Barrett played this part for three hundred nights without a break, and repeated his London success in W. G. Wills's Claudian which followed.
In 1884 he appeared in Hamlet, but soon returned to melodrama, and though he had occasional seasons in London he acted chiefly in the provinces. In 1886 he made his first visit to America, repeated in later years, and in 1898 he visited Australia. During these years the London stage was coming under new influences, and Wilson Barrett's vogue in melodrama had waned.
But in 1895 he struck a new vein of success with his drama of religious emotion, The Sign of the Cross, which crowded his theatre with audiences largely composed of people outside the ordinary circle of playgoers. He attempted to repeat the success with other plays of a religious type, but not with equal effect, and several of his later plays were failures.