The first edition of the score was completed in 1866. Verdi wrote Don Carlo for Paris and had to obey the genre requirements of the French "grand opera". The premiere took place on the 11th of March 1867, and the first alterations were already taking place: part of the music was cut, and ballet was added in the third act. Subsequently, the composer reworked the music many times. In 1872, the premiere of the "Naples" version of the opera took place, and the last, "Modena" version appeared in 1886. The four-act "Milan" version, which was released in 1884, is performed more often than the others.

Don Carlo refers to the mature period of Verdi's work and marks the transition from the violent bubbling up of emotions in La Traviata, Rigoletto and Il Trovatore to the deep psychologism of his later works. The libretto is based on the drama of the same name by Friedrich Schiller, whose work Verdi has repeatedly addressed before (Giovanna d'Arco, I masnadieri, Luisa Miller). The work of Schiller, like that of Hugo and Shakespeare, was one of the examples of dramatic mastery to Verdi, and he fully realized his aspirations in Don Carlo.