Sneezing typically occurs when foreign particles or sufficient external stimulants pass through the nasal hairs to reach the nasal mucosa. This triggers the release of histamines, which irritate the nerve cells in the nose, resulting in signals being sent to the brain to initiate the sneeze through the trigeminal nerve network. The brain then relates this initial signal, activates the pharyngeal and tracheal muscles and creates a large opening of the nasal cavity, resulting in a powerful release of air and bioparticles. The reason behind the particularly powerful nature of a sneeze is attributed to its involvement of not simply the nose and mouth, but numerous organs of the upper body – it is a reflectory response that involves the muscles of the face, throat, and chest.

An alternative cause of sternutation is sudden exposure to bright light - a bodily attribute known as the photic sneeze reflex. Up to 37 percent of individuals are believed to have this particular genetic trait, which is most commonly related to exposure to direct sunlight.

A rarer alternative trigger, observed in some individuals, is the fullness of the stomach immediately after a large meal. This is known as snatiation and is regarded a medical disorder passed along genetically as an autosomal dominant trait.

Sneezing cannot occur during sleep due to REM atonia - a bodily state wherein motor neurons are not stimulated and reflectory signals are not relayed to the brain. Sufficient external stimulants, however, may cause a person to wake from their sleep for the purpose of sneezing, although any sneezing that would occur afterwards would take place with at least a partially awake state of mind.