Despite the separation from his family and the harsh conditions imposed by war, Prokofiev remained prolific. He completed his 'War' sonatas for the Piano (Nos. 6, 7 and 8). He wrote his most sweeping opera yet, War and Peace, based on Tolstoy's monumental novel. Prokofiev's treatment was equally monumental. It would take him nearly ten years to complete the work. He also began sketches for another opera, Khan Buzay, but later abandoned it. During this time, Prokofiev also wrote incidental music for four films, the epic Cinderella ballet, a number of Symphonic Suites, the String Quartet No. 2, a Sonata for Flute and Piano, a transcription of that same Flute Sonata for Violin and Piano (made at the request of violinist David Oistrakh) , two military Marches, several folk songs, and the towering Fifth Symphony. This is an amazing string of works by any measure.

The 'War' sonatas are magnificent in their dynamism and span, almost orchestral in their sonority. The Sixth Sonata has emerged over the years as Prokofiev's most oft-recorded sonata. He gave the premiere performance himself in a Moscow Radio broadcast in 1940. By the time the Seventh Sonata was completed in 1942, Prokofiev's health had deteriorated for many reasons and he was unable to premiere the work. Sviatoslav Richter was selected to debut the work, which he did in 1943. The motoric Third Movement is the pinnacle of Prokofiev's 'toccata' line, unrelenting in its rhythm and power. He was awarded his first Stalin Prize for the Seventh Sonata. When the Eighth Sonata was completed in 1944, Prokofiev was again unhealthy enough to play the premiere. This time he selected another brilliant young Soviet pianist, Emil Gilels, in his stead. Gilels premiere performance came on 29 December 1944. Although not as popular as the Sixth and Seventh, the Eighth Sonata stands as perhaps the greatest of the cycle. Richter called it "the richest of all of Prokofiev's sonatas. It has a complex inner life with profound contrapositions."

The Second String Quartet also was extremely successful. Prokofiev's lifelong friend Miaskovsky, ever critical and never one to mince words, called it simply "magnificent music."

Cinderella, second only to Romeo and Juliet in popularity among Prokofiev's ballets, followed a circuitous route to its premiere on the Bolshoi stage in 1945. The work was originally commissioned by the Kirov Theater just prior to the outbreak of the German invasion. Prokofiev was in fact working on the piano score to the second act of the ballet when the invasion began. The tumultuous days after the invasion placed the project on hold. In fact, Prokofiev laid aside the work for two years to focus his energies on the opera War and Peace and other smaller works. When Prokofiev resumed work on Cinderella at the end of 1943, he completed a set of piano transcriptions (Opus 95 and 97) before he completed the orchestration (he completed a third set of piano transcriptions later as Opus 102.) The ballet received its premiere on 21-November-1945 in Moscow, with famed ballerina Galina Ulanova in the title role. Ulanova had danced the lead in Romeo and Juliet as well. The premiere was enormously well received, and its premiere by the Kirov in Leningrad five months later was also successful.

But of all the works in the wartime period, the most successful is his Fifth Symphony. Work began on the Fifth Symphony in 1944 immediately after he completed the orchestral score for Cinderella:

I wrote my Fifth Symphony in the summer of 1944 and I consider my work on this symphony very significant both because of the musical material put into it and because I returned to the symphonic form after a sixteen-year interval. The Fifth Symphony completes, as it were, a long period of my works. I conceived it as a symphony of the greatness of the human spirit.