The word "varmint" is an American version of "vermin," meaning the wild creatures that eat the crops and animals people raise for food. In the 21 st century most North Americans tend to think of varmints as smaller animals, but among my friends are a Montana ranching couple who recently had a 600-pound grizzly bear start killing their sheep, something the bear had previously done on nearby ranches. A state game warden ended up shooting the bear with a .300 Weatherby, not usually considered a varmint round.
Smaller varmints used to be taken care of primarily by the sons of farmers and ranchers. Their fathers were usually too tired after a long working day to hunt varmints, so gave their kids (who'd just spent the day sitting in school) a cheap .22 rimfire and told them to go shoot crows, prairie dogs and foxes.
There was a time when this seemed the natural order of country life, but eventually industrial America and college educations pulled many kids away from farms. World War I accelerated this change, because many of the soldiers who'd seen Europe refused to settle down again to grow corn or cows--though some kept coming back home to shoot varmints.
Naturally the more avid shooters started developing their own cartridges, and naturally the big factories took notice. The first genuine varmint wildcat to be legitimized was the .22 Hornet, among the few cartridges ever mass-manufactured before a factory rifle appeared. Winchester started making ammunition in 1930, but didn't start chambering their Model 54 rifle for the Hornet until 1932.
The .22 Hornet was developed, at least partially, at Springfield Armory, where a gun-writing soldier named Townsend Whelen was part of the team. The Army thought there might be some use for the tiny round, and it turned out there was. Eventually the military built "survival rifles" in .22 Hornet for pilots who flew in remote regions.
The .22 Hornet was an instant success, even in the beginning of the Great Depression. Most avid varmint shooters handloaded, and the little cartridge was very economical to reload, using a small charge of Hercules 2400, a powder developed specifically for the Hornet case and named for the muzzle velocity produced.
The 40 years after the introduction of the .22 Hornet saw the commercialization of several other varmint-inspired wildcats, including the .219 Zipper (a necked-down .25-35) and the .22-250 Remington. The factories themselves, including the .222 Remington and .220 Swift, developed other varmint rounds. The .222 eventually led to the .223 Remington, the civilian version of the 5.56mm NATO. The .220 Swift was the fastest commercial cartridge for the entire 20th century, and hasn't been beaten by much even today.
Please note that all of these cartridges were .22 caliber. Twenty-two centerfires were always considered the most practical varmint rounds; despite efforts by major companies to sell 6mm and 25-caliber rounds as "combination" cartridges, useful both for varmints and deer-sized game. Most shooters eventually learned that while the .243 Winchester and...