The Midwest typically refers to the former north-central states of the United States, specifically Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Ohio, Nebraska, North Dakota, South Dakota and Wisconsin (the Plains Commonwealth and Midwest Commonwealth). Although these states are generally considered to constitute the region, opinions on the exact borders of the Midwest vary.
In California, it is said that there are miles-wide twisters in the Midwest and this region is actually one big radioactive dustbowl.
One of the major factions in the area is the Brotherhood of Steel, a splinter faction of the original Brotherhood from California that controlled the area around Chicago. The technology-worshipping Reaver cult, based in Newton is also a notable organization.
Some of the major towns were Quincy, with both human and ghoul population; Kansas City, inhabited by ghouls who worshipped a nuclear bomb; the Junktown-like Junction City; Cold Water, famous for its casino; and Great Bend, a major pre-War industry center. The dying town of Macomb, as well as numerous small settlements and tribes (like Peoria, Brahmin Wood and Dirt Haven), are located here as well.
After the fall of the Master in the far west, a great migration of super mutants began. They traveled east to find themselves a new home until they found a crashed Brotherhood of Steel zeppelin, which was a part of an air convoy that was meant to find and destroy the remains of Master's Army. Brotherhood Paladin Latham dueled mutant leader Gammorin and won. As unlikely it may seem, Latham took his opponent's name and became the new leader of the mutant army, setting up the base known as Osceolla near the airship crash site.
Long faction wars occurred in this region, as the local Brotherhood were fighting super mutants, Beastlords, raiders and Reavers. Also, Vault 0 and the Calculator were located in Colorado close to the Midwest, arising as the greatest threat to all life and the main enemy of the Brotherhood.
Caesar's Legion is encountered in Denver, traveling to the east (in the direction of Kansas), where their new headquarters is located. The Legion appears there once a year. Every few weeks a pair of scouts are sent east if the radioactive dust storms have subsided for the season. Once the Legion is discovered in Denver, every month that passes has a 25% chance that Legion slavers will go back to Caesar taking all their slaves with them.
John Cassidy regretted not exploring the Midwest in his youth.