His father was a successful theatre manager and in March 1803 he was sent away to Rugby School. The plan was for him to be educated for "a more respectable profession than the stage". Unfortunately his father encountered serious business problems and had to withdraw his son from the school in 1808 with a debt of over £100 for school fees.
William Macready was imprisoned for debt but on his release in 1810 he resumed his career in theatre management. A few weeks later the young Macready appeared as Romeo in his father's production of Romeo and Juliet. According to his biographer, Richard Foulkes : "After a faltering, mechanical start, Macready, encouraged by sympathetic applause from the audience, got the measure of his role and achieved what the audience, the critics, and the young actor himself recognized as a remarkable début. During the next four years as the juvenile lead in his father's company he played more than seventy different roles."
Macready was soon appearing with some of the most famous actors of the time. This included Sarah Siddons, John Philip Kemble, Dorothy Jordan and Charles Mayne Young. The theatre critic, William Archer, claims that Sissons gave him some important advice while performing together: "You are in the right way, but remember what I say: study, study and do not marry till you are thirty!" Macready was such a popular actor he was able to command a salary of £50 a week.
In 1815 Macready was in Glasgow when he met a pretty nine-year-old girl, Catherine Frances Atkins. He took a strong interest in her career as a young actress and they appeared in several plays together.
In September 1816 he accepted a five year contract to appear in Covent Garden. At first he received some negative comments about his acting. James Leigh Hunt described him as: "One of the plainest and most awkwardly made men that ever trod the stage. His voice is even coarser than his personage". However, he was extremely popular with the public and had great success in Romeo and Juliet, Othello, Richard III and King Lear. In 1820 he made his début as Macbeth .
In 1822 Charles Kemble became the new co-proprietor of Covent Garden. Unhappy with the new management, Macready terminated his contract and moved to Drury Lane, at a salary of £20 a night. Macready appeared at Drury Lane for the next thirteen years. According to most critics, he was unable to reach the standards he had set when he first arrived in London.
Macready married his long-term companion, the 18 year old Catherine Frances Atkins, at St Pancras Church on 24th June 1824. He took his new wife to the United States and appeared in several productions in New York City, Boston, Baltimore, Philadelphia and Albany. On 7th April 1828 Macready appeared in Paris as Macbeth . Later that year he played Hamlet and Othello in the city.
Peter Ackroyd has argued: "He was the most famous Shakespearean actor of his day... He was in some ways acutely theatrical, with an expressive face, a powerful voice, and sonorous manner... Although Macready took on the great roles, he seems to have been better at those expressing passion rather than nobility; he was a master of pathos, remorse, the more bravura aspects of melodrama... Macready was very intelligent, if inclined to be short-tempered."
Macready was now the highest paid actor of his generation. In 1828 he received an income of £2,361 for his performances. He was now in a position to financially support a family and his first child, Christina Laetitia, was born on 26th December 1830. However, the years following saw a slight dip in his income as Alfred Bunn, took control of London's two main theatres (Covent Garden and Drury Lane). Macready disliked Bunn and only made fifteen appearances on the stage in 1833. The conflict continued and during a production of Richard III on 29th April 1836, Macready denounced Bunn as a "damned scoundrel" and struck him in the face. The two men started fighting and had to be separated by other members of the company. Bunn sued Macready for assault and eventually he won damages of £150.
In 1836 the 18-year-old Helen Faucit joined Macready's theatre company. It was soon rumoured that he was having an affair with Faucit. His biographer, Richard Foulkes , has pointed out: "The young actress's nightly visits to Macready's room after the performance were avowedly for help with her studies, but even Macready could not entirely discount his protégée's feelings for him or suppress completely his own susceptibility to what he described, in a poem inscribed in her album, as Miss Faucit's holier charm."
Macready became friends with a group that included Charles Dickens , John Forster, William Makepeace Thackeray, William Wordsworth , Thomas Carlyle , Jane Carlyle and Robert Browning. He asked Browning to write him a play. The result, Strafford , was performed on 1st May 1837. After the bankruptcy of Alfred Bunn , this group encouraged Macready to take over the lease of Drury Lane . After refurbishments, the first production, The Merchant of Venice, opened 27th December 1841. Although his productions received good reviews it was not a profitable venture.
In December 1844, Macready and Helen Faucit went on tour to Paris where they gave performances of Hamlet , Othello and Macbeth . They received favourable comments from Victor Hugo, Théophile Gautier, George Sand, Eugène Delacroix and Alexandre Dumas.
Macready's tour of the United States in 1848 was less successful. The main reason for this was a long-standing dispute with America's leading actor, Edwin Forrest. It has been argued that hostility to Macready was partly a response to unfavourable accounts of the country by two of his friends, Frances Trollope and Charles Dickens.
In Cincinnati, one of Macready's opponents, arranged for an animal carcass to be thrown on stage. During the performance of Macbeth at the Astor Place Theatre, in New York City, on 7th May, Macready was attacked with eggs, apples and potatoes. The militia were called out to deal with the disturbance and they opened fire on the audience, killing twenty-three people.
Macready final performance took place at Drury Lane on 26th February 1851. He retired to his house in Sherborne, Dorset. On 18th September 1852 his wife died unexpectedly while the couple were visiting Plymouth. At the age of sixty-seven, he married Cecile Louise Frederica Spencer (1827–1908). A son, Cecil Frederick Nevil Macready, was born in 1862.