In World War II, the Marines played a central role in the Pacific War; the Corps expanded from two brigades to two corps with six divisions and five air wings with 132 squadrons. In addition, 20 defense battalions and a parachute battalion were set up. The battles of Guadalcanal, Tarawa, Cape Gloucester, Saipan, Peleliu, Iwo Jima, and Okinawa saw fierce fighting between U.S. Marines and the Imperial Japanese Army.

Philip Johnston proposed the use of Navajo the United States Marine Corps at the beginning of World War II. The idea was accepted, and the Navajo code was formally developed and modeled on the Joint Army/Navy Phonetic Alphabet that uses agreed-upon English words to represent letters. For each letter in the English alphabet, the code talkers were asked to generate several nouns and sometimes verbs in Navajo using the principle of letter and word substitution. As it was determined that phonetically spelling out all military terms letter by letter into words—while in combat—would be too time consuming, some terms, concepts, tactics and instruments of modern warfare were given uniquely formal descriptive nomenclatures in Navajo (the word for "potato" being used to refer to a hand grenade, or "tortoise" to a tank, for example).

During the battle of Iwo Jima, photographer Joe Rosenthal took the famous photograph Raising the Flag on Iwo Jima of five Marines and one Navy Corpsman raising the American flag on Mt. Suribachi. Secretary of the Navy James Forrestal, who had come ashore earlier that day to observe the progress of the troops, said of the flag raising on Iwo Jima, "...the raising of that flag on Suribachi means a Marine Corps for the next five hundred years." The acts of the Marines during the war added to their already significant popular reputation. The USMC War Memorial in Arlington, Virginia was dedicated in 1954. By war's end, the Corps had grown to include six divisions, five air wings, and supporting troops totaling about 485,000. Nearly 87,000 Marines were casualties during World War II (including nearly 20,000 killed). and 82 received the Medal of Honor, 2,274 Marines were POWs {2,270 by the Japanese and 4 by the Germans}; 1,756 returned to the USA. 268 known to have died and 250 known to have been captured but otherwise unaccounted for and presumed to have died.