This disclosure relates to cartridges, including shotshell cartridges, for launching multiplex projectile loads that contain different sizes or types of projectiles, and methods of loading the cartridges. In one aspect, for example, the present cartridges can contain an obturating component adjacent the cartridge propellant, a first payload adjacent the obturating component, a separating component adjacent the first payload, and a second payload adjacent the separating component. Shotshells of this configuration in which the first (aft) payload comprises birdshot and the second (forward) payload comprises buckshot are particularly useful.