In 1957, one year after Winchester announced the .458 Winchester Magnum cartridge in the Model 70 rifle, Weatherby responded with the .460 Weatherby Magnum based on the .378 Weatherby Magnum (circa 1953) case necked to accept .458-inch bullets. Advertised velocities pushed a 500-grain bullet to 2,700 fps, some 500 to 600 fps faster than the .458 Winchester Magnum and generated over 8,000 foot-pounds of energy. It was hailed as "The world’s most powerful commercial sporting cartridge." Today, it ranks as one of the most powerful sporting cartridges having been surpassed by the comparatively new .700 Nitro Express and a few specialized proprietary cartridges. Regardless, it delivers a heavy blow and is suitable for any game on earth.

Currently Weatherby has reduced pressures and velocities slightly, resulting in a 500-grain RN softpoint or solid bullet at 2,600 fps, or Barnes 450-grain TSX at 2,660 fps. In a Weatherby Mark V fitted with a 26-inch barrel, factory load velocities were very close to advertised figures with the 500-grain RN reaching 2,577 fps and the 450-grain clocking 2,644 fps.

Beginning in 1994, the .460 Weatherby Magnum became a SAAMI standard cartridge with a maximum average pressure of 65,000 psi. Using the Hornady 350-grain RN bullet, Hodgdon Varget reached over 3,000 fps and was the most accurate powder with that bullet. With the Hornady 500-grain DGS, Vihtavuori N-160 and Alliant Reloder 19 powders reached over 2,500 fps, and both produced sub-MOA, 100-yard groups.

To obtain correct powder ignition, Federal 215 Large Rifle Magnum primers were used. To keep bullets in place when subjected to heavy recoil, a heavy roll crimp is suggested.