[10] The cartridge can be extremely accurate to 300 yards (270 m) and beyond, but may not retain enough terminal energy to reliably drop medium game at that distance.

[7][11][13] Besides hunting applications, the cartridge is popular with target and metallic silhouette shooters for those same recoil and velocity properties, with superb accuracy.

[2] Gun Digest estimates that (as of the end of 2018) the .243 Winchester is the second-most popular of all hunting rifle chamberings (after the long action .30-06).

[17] Well-regarded Field and Stream editor and Harvard-educated[18] technical gun enthusiast Warren Page began experimenting with wildcatting a .243 caliber (6.2mm) round in the 1940s sometime after the 6mm Lee Navy was discontinued.

[20] It was a ground-breaking development with at first only two factory loads, combining a versatile and effective combination of 80-grain bullets optimized for high-velocity, long-range performance for varmint hunters (e.g., groundhogs, coyotes, prairie dogs) and 100-grain bullets suitable for game up to the size of deer and pronghorn antelope.

In a non-sporting context, bolt-action rifles chambered for the .243 were utilized by the Los Angeles Police Department's special weapons and tactics (SWAT) unit during its early years.

[26] Lack of overpenetration on medium game has traditionally been perceived either as a problem (lack of exit wounds and blood trails[2]) or as a feature ("uses up all the energy in the deer"[13]) of traditional lead .243 cartridges versus larger and heavier rounds, but monolithic copper .243 ammunition weighing as little as 80 grains (5.2 g) negates this characteristic and causes adequate penetration and blood trails through even larger-bodied medium game like wild hogs.

[3] The .243 produces a velocity of 3,200 feet (980 m) per second from factory-loaded expanding monolithic copper projectiles weighing 85 grains (5.5 g) fired from a 24-inch (610 mm) barrel.