The musketeers typically carried matchlock muskets, smooth bore muzzle loading firearms. These worked by a slow burning cord or 'match' set off the priming charge of fine gunpowder in the ‘pan’ and thus, via the ‘touch hole’, the main charge in the barrel. According to Gentilini (1598) the musket bullet would carry up to 2000 yards (fired at 45 degrees elevation) but when fired level ('dritta linea') the range was 100 yards. Because they were highly inaccurate weapons and to achieve the most effective killing power, the muskets were typically fired a point blank range or closer. It was the slow speed of loading as well as the inaccuracy of the weapon that were key limiting factors in the way in which the armies of the period fought (see the sequence of images for the loading and firing of a musket in the image gallery).

To keep up a steady rolling fire the musketeers might fire by rank, each rank firing and then moving to the rear or being replaced to the fore, as the other five ranks reloaded. Alternatively, and a tactic increasingly commonly used during the war, the musket could fire in a single salvo at close range, having a devastating effect on an advancing battalion. However, particularly with inexperienced musketeers, the fire often went too high and so missed its target altogether, perhaps explaining to some degree why casualty figures are often fairly low in Civil War battles. In hand to hand fighting the musketeer might resort to the use of the sword but English musketeers were noted for more often using the butts of their muskets as clubs.

For safety reasons, those guarding the train of artillery were provided with 'firelocks', flintlock muskets in which the charge was ignited by a spark produced as a flint struck a metal plate to set off the priming charge. Flintlocks were also carried by some other specialist musketeers, such as the companies of firelocks which Prince Rupert used to ride double mounted with some of his cavalry in order to interline with the cavalry deployment to exploit the far greater range and penetration of the musket bullet compared to the pistol or carbine bullet.