Vash wields a massive revolver as his main weapon like in the original series. The caliber has apparently been scaled down from .45 Long Colt to .22, based on Vash asking the townsfolk for .22 bullets in "Noman's Land".
Roberto's Derringer
Roberto de Niro carries a double-barreled Derringer as his main weapon.
Golden Pistol
Chuck Lee, the captain of the July City Military Police wields a golden pistol with a laser sight as his sidearm in "Noman's Land".
The Heckler & Koch MP7 is the main submachine gun used by Eye of Michael cultists.
M3 Grease Gun
Rosa and other Jeneora Rock residents are seen carrying M3 Grease Guns in "The Running Man". The Bad Lads Gang are also seen carrying Grease Guns in "Once Upon a Time in Hopeland".
Livio's Submachine Guns
Livio the Double Fang carries four submachine guns with two each arranged in a cross-shaped pattern similar to Wolfwood's Punisher.
Rifles
Unknown Rifles
Launchers
RPG-7
Nebraska is seen carrying an RPG-7 fitted with a tandem warhead in "The Running Man".
Cluster Missile Launcher
Chuck Lee uses a launcher to fire a cluster missile during his duel with Vash in "Noman's Land".
Others
Wolfwood's Punisher Cross
Nicholas D. Wolfwood carries his iconic giant cross-shaped weapon platform called the "Punisher" in the series. The Punisher consists of a machine gun and a laser cannon.
Monev the Gale's Gatling Guns
Monev the Gale is armed with two arm-mounted gatling guns like in the original series.