Quake 4 features ten firearms and ammunitions.
| Weapon | Damage | Ammo Type | Magazine Size | Maximum Ammo | Fire Mode | Rate of Fire |
| Blaster | 8, 50 (Charge) | Battery | ∞ | ∞ | Semi-auto | ~360 rpm |
| Machine Gun | 15, 20 (Scope) | Bullets | 40, 80 (Upgrade) | 300 | Automatic | 545 rpm |
| Shotgun | Up to 140 | Shells | 8, 10 (Upgrade) | 50 | Pump-action | ~84 rpm |
| Hyperblaster | 14 | Batteries | 60 | 400 | Automatic | 750 rpm |
| Grenade Launcher | Up to 125 | Grenades | 8 | 50 | Semi-auto | 75 rpm |
| Nailgun | 25 | Nails | 50, 100 (Upgrade) | 300 | Automatic | 375 rpm |
| Rocket Launcher | Up to 150 | Rockets | 1, 3 (Upgrade) | 40 | Semi-auto | 75 rpm |
| Railgun | 125 | Slugs | 3 | 50 (35 in MP) | Semi-auto | 37.5 rpm |
| Lightning Gun | 11 | Lightning Coils | - | 400 (300 in MP) | Automatic | 960 rpm |
| Dark Matter Gun | 200 + 50 per second | Dark Matter Cores | - | 25 | Single | 15 rpm |