With his company, Barrett is credited with attracting the largest crowds of English theatregoers ever because of his success with melodrama, an instance being his production of The Silver King (1882) at the Princess's Theatre of London.

Though Barrett had occasional seasons in London he acted chiefly in the provinces, with his company being one of the most successful of the decade, receiving a £2,000 average yearly profit just from the Grand Theatre Leeds.

By the 1890s, the London stage was already coming under new influences, and Wilson Barrett's vogue in melodrama had waned, leaving him in financial difficulties.

Still there in 1895, Barrett found fortune again with a production [7] which would effectively become his most successful, the historical tragedy The Sign of the Cross—which was originally produced in the United States at the Grand Opera House, St. Louis, Missouri on 28 March 1895;[8] in the United Kingdom, at the Grand Theatre, Leeds, on 26 August 1895;[9] in London, at the Lyric Theatre, London on 4 January 1896;[10] and in Australia, at Her Majesty's Theatre, Sydney on 8 May 1897[11]—in which Barrett played Marcus Superbus, an old Roman patrician of the years of Nero, who falls in love with a young woman, Mercia (originally played by Maud Jeffries) and converts to Christianity for her, both sacrificing their lives in the arena to the lions.

[citation needed] The theatre was crowded with audiences largely composed of people outside the ordinary circle of playgoers, shepherded by enthusiastic local clergymen.

Thanks largely to the success of the Sign of the Cross, he left £57,000, even after periods of relative failure, mainly during his later years managing the Old Court Theatre.

The Victoria & Albert Museum Theatre and Performance Archives holds designs by Edward William Godwin for Barrett's productions of Juana, Claudian, Hamlet, Junius, and Clito.

In 1932, Cecil B. DeMille produced and directed a highly successful film version of The Sign of the Cross, starring Fredric March as centurion Marcus Superbus, Claudette Colbert as Poppea, Charles Laughton as Nero, and Elissa Landi as Mercia, the Christian woman with whom Marcus falls in love.