La favorita started life in French as a work for the Parisian Théâtre de la Renaissance, titled L'ange de Nisida. Due to the ill-timed bankruptcy of that theater, it was never produced, but Donizetti managed to parlay the failed effort into a new work for the Paris Opéra in 1840. For this new production, the esteemed French librettist Eugène Scribe adapted Alphonse Royer and Gustave Vaëz's original libretto, shifting its focus to the touching story of Léonor de Guzman, favored mistress of King Alphonse XI of Castille. These skillful alterations allowed Donizetti to preserve the lion's share of his original score, which contains some of the finest music of his career. The entire fourth act and most of the first three survived the transition intact; the primary changes were the composition of new arias, more suitable for the new drama as well as for the first cast at the Opéra. The premiere took place on December 2, 1840, and was an incredible triumph for both singers and composer. The work is a big grand opera in the classic French mold, with ballets, pageantry, ceremony, and large choral scenes, combining a historical and religious setting with a passionate love story. The many moods and colors of the opera are enhanced by the sheer beauty of Donizetti's melodies. The drama is powerful and moving, with full-blooded, complex characters.

The work is a tragedy built around the ill-fated love affair between the king's mistress, Léonor, and a young novice monk, Fernand, who, not knowing her true identity, betrays his vows to pursue her. Frustrated by circumstance, obligation and misunderstanding, their love is realized only at her death. Highlights from the score include the two lovers' impassioned duets from the first and last acts ("Mon idole" and "Viens, viens, je cède éperdu"), as well as Fernand's famous fourth-act aria, "Ange si pur" (better-known in its Italian version, "Spirto gentil"). On the whole, the score shows Donizetti at his most consistently inventive and resourceful.

The score was a hit at the Paris Opéra and was performed consistently until the early twentieth century. Since that time it has receded in its native France and become more widely known in its Italian translation. The use of different translations and performing editions has led to considerable corruption of Donizetti's original score and has somewhat eroded critical opinion of the work, but it has always held a place in the repertory.