P-40s were used pretty extensively in the Pacific theater, most notably in the Pacific Southwest and China-Burma-India(CBI). In the latter theater, the use of the P-40 by the American Volunteer Group (AVG), sometimes called the Flying Tigers, helped to immortalize the fighter. The P-40 arguably was also the most modern fighter in the Army Air Corps arsenal in 1941, which meant that a number of USAAF units in the Philippines and the Dutch East Indies used the fighter. The relatively advanced nature of the P-40 proved both a blessing and a curse in the period of initial Japanese conquests. When the P-40 worked, its performance was more than equal to its Japanese opponents, but a number of mechanics were inexperienced with the type and spares were either lost during the Japanese advance or were never sent to their units in the chaotic logistics before the balloon went up. When coupled with both the inexperience of their pilots and the overall numerical superiority of the Japanese, the P-40s did little to stem the flow of the Japanese advance.

The P-40 generally had more success in the Pacific theaters than in other corners of the conflict. Both the RAF and the USAAF used them in North Africa, but that was more out of necessity than choice. The P-40 was the only frontline fighter available in quantity at the start of American involvement in the war (ie just prior to Pearl Harbor with Lend-Lease), and could be supplied to RAF forces in Egypt via a long air supply route over central Africa. The P-40's poor high altitude performance meant it would have no real role in operations in NW Europe. It found some success in the USSR, but the type's Allison engines did not perform very well during the cold Russian winters. The peculiarities of the P-40's airframe limited the amount of upgrading the machine would receive during the war; P-40 models up-engined with Merlins only achieved a marginal boost in speed. But these upgraded P-40s often made their way to the SW Pacific and CBI, where the USAAF air groups were much lower on the totem pole for newer equipment than other theaters. Although the P-40 served in most of the theaters during the conflict (including stateside, where it was an advanced trainer), its swansong as a frontline aircraft was in the Pacific.