Cesarius-Benjaminus (Цезарий-Вениамин) Cui was born in Vilnius, Vilna Governorate, Russian Empire (now Vilnius, Lithuania), to a Roman Catholic family, the youngest of five children. His French father, Antoine (his name was later Russified as Anton Leonardovich), had entered Russia as a member of Napoleon's army in 1812, settled in Vilnius upon their defeat, and married a local woman named Julia Gucewicz. The young César grew up learning French, Russian, Polish, and Lithuanian. Before finishing gymnasium, in 1850 Cui was sent to Saint Petersburg to prepare to enter the Chief Engineering School, which he did the next year at age 16. In 1855 he was graduated from the Academy, and after advanced studies at the Nikolaevsky Engineering Academy, now Military engineering-technical university, he began his military career in 1857 as an instructor in fortifications. His students over the decades included several members of the Imperial family, most notably Nicholas II. Cui eventually ended up teaching at three of the military academies in Saint Petersburg. Cui's study of fortifications gained from frontline assignment during the Russo-Turkish War of 1877-1878 proved quite important for his career. As an expert on military fortifications, Cui eventually attained the academic status of professor in 1880 and the military rank of general in 1906. His writings on fortifications included textbooks that were widely used, in several successive editions (see bibliography below).

Two personalities of direct significance for Cui were women who were specially devoted to his music. In Belgium, the Comtesse de Mercy-Argenteau (1837–1890) was most influential in making possible the staging there of Prisoner of the Caucasus in 1885. In Moscow, Mariya Kerzina, with her husband Arkadiy Kerzin, formed in 1896 the Circle of Russian Music Lovers, a performance society, which began in 1898 to give special place to works by Cui, among those of other Russian composers, in its concerts.

Despite his achievements as a professional military academic, Cui is best known in the West for his 'other' life in music. As a boy in Vilnius he received piano lessons, studied Chopin's works, and began composing little pieces at fourteen years of age. In the few months before he was sent to Petersburg, he managed to have some lessons in music theory with the Polish Composer Stanisław Moniuszko, who was residing in Vilnius at the time. Cui's musical direction changed in 1856, when he met Mily Balakirev and began to be more seriously involved with music.

Cui married Mal'vina Rafailovna Bamberg (Мальвина Рафаиловна Бамберг) in 1858. He had met her at the home of Alexander Dargomyzhsky, from whom she was taking singing lessons. Among the musical works Cui dedicated to her is the early Scherzo, Op. 1 (1857), which uses themes based on her maiden name (BAmBErG) and his own initials (C. C.), and the comic opera The Mandarin's Son. César and Mal'vina had two children, Lidiya and Aleksandr. Lidiya, an amateur singer, married and had a son named Yuri Borisovich Amoretti; in the period before the October Revolution Aleksandr was a member of the Russian Senate.

Even though he was composing music and writing music criticism in his spare time, Cui turned out to be an extremely prolific Composer and feuilletonist. His public "debut" as a Composer occurred 1859 with the performance of his orchestral Scherzo, Op. 1, under the baton of Anton Rubinstein and the auspices of the Russian Musical Society. In 1869 the first public performance of an opera by Cui took place; this was his William Ratcliff (based on the tragedy by Heinrich Heine); but it did not ultimately have success, partially because of the harshness of his own writings in the music press. All but one of his operas were composed to Russian texts; the one exception, Le flibustier (based on a play by Jean Richepin), premiered at the Opéra-Comique in Paris in 1894 (twenty-five years after Ratcliff), but it did not succeed either. Cui's more successful stage works during his lifetime were the one-act comic opera The Mandarin's Son (publicly premiered in 1878), the three-act Prisoner of the Caucasus (1883), based on Pushkin, and the one-act Mademoiselle Fifi (1903), based on Guy de Maupassant. Besides Flibustier, the only other operas by Cui performed in his lifetime outside of the Russian Empire were Prisoner of the Caucasus (in Liège, 1886) and the children's opera Puss in Boots (in Rome, 1915).

Late in life Cui's presumed progressiveness as espoused in the 1860s and '70s faded, and he showed firm hostility towards the younger "modernists" such as Richard Strauss and Vincent d'Indy. Cui's very last published articles (from 1917) constituted merciless parodies, including the little song "Hymn to Futurism" and "Concise Directions on How to Become a Modern Composer of Genius without Being a Musician".

As a Writer on music, Cui contributed almost 800 articles between 1864 and 1918 to various newspapers and other publications in Russia and Europe. (He "retired" from regular music criticism in 1900.) His wide coverage included concerts, recitals, musical life, new publications of music, and personalities. A significant number of his articles (ca. 300) dealt with opera. Several of his themed sets of articles were reissued as monographs; these covered topics as varied as the original 1876 production of Wagner's Der Ring des Nibelungen in Bayreuth, the development of the Russian romance (art song), music in Russia, and Anton Rubinstein's seminal lectures on the history of piano music of 1888–1889. (See list of writings below.) In addition, as indicated above as part of his profession, Cui also published many books and articles about military fortifications.

Cui's works are not so nationalistic as those of the other members of The Five; with the exception of Pushkin, his operas do not display a strong attraction to Russian sources. In the area of art song, however, the vast majority of Cui's vocal music is based on Russian texts. Overt attempts at Russian "folk" musical style can be detected in passages from his first act of the collaborative Mlada (1872), The Captain's Daughter, a couple of the children's operas, and a few songs; many other passages in his music reflect the stylistic curiosities associated with Russian art music of the 19th century, such as whole tone scales and certain harmonic devices. Nevertheless, his style is more often compared to Robert Schumann and to French composers such as Gounod than to Mikhail Glinka or to Cui's Russian contemporaries.

Cui's primary goal as a critic was to promote the music of contemporary Russian composers, especially the works of his now better-known co-members of The Five. Even they, however, were not spared negative reactions from him here and there, especially in his blistering review of the first production of Mussorgsky's Boris Godunov in 1874. (Later in life Cui championed the music of this late colleague of his, to the point of making the first completion of Mussorgsky's unfinished opera The Fair at Sorochyntsi.)

In such a long and active musical life as Cui's there were many accolades. In the late 1880s and early 1890s several foreign musical societies honored Cui with memberships. Shortly after the staging of Le flibustier in Paris, Cui was elected as a correspondent member of the Académie française and awarded the cross of the Légion d'honneur. In 1896 the Belgian Royal Academy of Literature and Art made him a member. In 1909 and 1910 events were held in honor of Cui's 50th anniversary as a Composer.

Cui's activities in musical life included also membership on the opera selection committee at the Mariinsky Theatre; this stint ended in 1883, when both he and Rimsky-Korsakov left the committee in protest of its rejection of Mussorgsky's Khovanshchina. During 1896–1904 he was Director of the Petersburg branch of the Russian Musical Society.

In addition, Cui wrote many works for piano and for chamber groups (including three string quartets), numerous choruses, and several orchestral works, but his most significant efforts are reflected in the operas, of which he composed fifteen of varying proportions. Besides children's music (which includes four fairytale operas as well as the aforementioned songs), three other special categories of compositions stand out among his works: (1) pieces inspired by and dedicated to the Comtesse de Mercy-Argenteau (whom the Composer knew from 1885 to her death in 1890; (2) works associated with the Circle of Russian Music Lovers (the "Kerzin Circle"); and (3) pieces inspired by the Russo-Japanese War and World War I.

In 1916, the Composer went blind, although he was able to compose small pieces by dictation. Cui died on 13 March 1918 from cerebral apoplexy and was buried next to his wife Mal'vina (who had died in 1899) at the Smolensk Lutheran Cemetery in Saint Petersburg. In 1939, his body was reinterred in Tikhvin Cemetery at the Alexander Nevsky Monastery, Saint Petersburg, to lie beside the other members of The Five.