In 1836, Verdi married Margherita Barezzi, the daughter of his greatest benefactor, and completed his first opera, Rocester. The music from this work only survives in the composer's next opera, Oberto, Conte di San Bonifacio, which opened at La Scala in 1839.

His next opera, Un Giorno di Regno (King for a Day), was a complete failure and Verdi resolved to cancel his La Scala contract and give up music altogether. The manager of La Scala, Bartolomeo Merelli, persuaded him to persevere and write his next opera—Nabucodonosor (Nebuchadnezzar). This opera came to be called Nabucco and premiered in 1842 to great acclaim. His next two operas—I Lombardi alla Prima Crociata (The Lombards on the First Crusade) and Ernani—secured Verdi's reputation as a major figure in the music world.

Between 1844 and 1850 Verdi composed at a tremendous rate. Luisa Miller in 1849 and Stiffelio in 1850 demonstrate Verdi's maturing style and more flowing musical line. During his "middle period" Verdi wrote three of his most successful operas: Rigoletto (1851), Il Trovatore (1853), and La Traviata (1853).

In 1859, Verdi married his second wife, soprano Giuseppina Streponni. In that same year, Verdi wrote Un Ballo in Maschera (A Masked Ball) which, like several of his other works, aroused the ire of the censors who objected to the representation of a rebellion against a monarch. From 1861-65, after Napoleon III drove the Austrians from northern Italy, Verdi was elected to represent Busseto in the newly formed Italian parliament. During this time he wrote La Forza del Destino and Don Carlos.

In 1870, he accepted a commission to write an opera for the opening of the Suez Canal. The opera, Aida, was premiered in both Cairo and Milan in 1871. Following the success of Aida, Verdi retired to his estate Sant'Agnata. In 1875, the death of the great Italian novelist and patriot, Alessandro Manzoni, moved Verdi to complete a requiem mass that had originally been intended to honor his noted compatriot, Gioacchino Rossini.

His publisher, Giulio Ricordi, who introduced him to the celebrated Arrigo Boito, drew Verdi back to opera composing. Verdi and Boito both worked together on Otello, which premiered in La Scala in 1886. Verdi's last opera was the only other comedy he had written since the disastrous Un Giorno di Regno: Falstaff, considered Verdi's humanistic swan song.