The .378 Weatherby Magnum was designed by Roy Weatherby in 1953. It was an original belted magnum design with no parent case, inspired by the .416 Rigby and headspacing of the belted .375 H&H Magnum. The 215 magnum rifle primer was developed by Federal specifically for this round. The cartridge can hold upwards of 7.13 g of powder. The 378 Weatherby Magnum cartridge also has the double radius shoulder design found on the first and smaller proprietary line of Weatherby magnum cartridges.

The .375 Weatherby Magnum (9.5×73mmB) is a medium-bore rifle cartridge. The cartridge is blown out, improved and provided with the Weatherby double radius shoulder – given the Weatherby treatment – version of the .375 H&H Magnum. Unlike other improved versions of the .375 H&H Magnum like the .375 Ackley Improved, the .375 Weatherby Magnum is not a wildcat and existed as a proprietary cartridge until the CIP published specifications for the cartridge.