Chunks of pork and beef are combined with seasoning and a sodium nitrate based curing agent. A small amount of sugar is added to color and flavor the mixture, while at the same time acting as a fermentation agent and equalizer to the rising acid levels. The meat chosen for the mixture is low in acid--the acidity will raise as the pepperoni cures. The ingredients of the mixture are compounded--starting with the beef and ending with the sodium nitrate base.

After mixing, the pepperoni mixture is stuffed into casings--usually made with the intestinal tract from a pig or cow. The casings form the pepperoni mixture into links and keeps the mix together during the cooking phase. As pepperoni is considered a dry sausage, it is common to use more fibrous casing in the manufacturing of pepperoni. A mechanical stuffer is often used to stuff the pepperoni mix into the casings. After the mix is stuffed into the casing, each pepperoni-filled link of the casing is sectioned off with a piece of string or rope.

Prepared pepperoni is most often cooked in smoke houses or ovens at low temperatures to slowly dry and age the pepperoni links. The process of heating and drying the pepperoni may take days. Cooking is slow to avoid over-drying of the links. The casing of the pepperoni is porous enough to absorb the smoke and heat, letting the pepperoni be thoroughly cooked.