If the organism infects a wound where the oxygen concentration is low (interrupted vascularisation, foreign body, tissue necrosis, umbilical stump), the bacterium can multiply there. The bacterium itself is not invasive. The pathogenic organism produces a neurotoxin, tetanospasmin. This is released when the organism lyses. This protein is responsible for all the clinical manifestations of tetanus. The toxin is cleaved outside the cell by a bacterial protease into a heavy and a light chain. The toxin migrates via the peripheral nerves and/or via the lymphatics and the blood to the central nervous system. The heavy chain binds to disialogangliosides. The light chain of the neurotoxin of C. tetani is a zinc endopeptidase which acts in the spinal cord on the inhibitory synapses which modulate the motor reflex arc. There the toxin cleaves the protein synaptobrevin which is present on the presynaptic vesicles which contain the inhibiting neurotransmitters GABA and glycine. Due to the removal of synaptobrevin on the exterior of the vesicles, the latter can no longer fuse with the synaptic membrane. Therefore the reflex arc cannot be inhibited. The consequence of the removal of the normal inhibition of the motor neurones is an increased muscle tone at rest and tonic spasms. The toxin is also active on the sympathetic nervous system. The role of a second toxin, tetanolysin, is still unclear.

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It is one of the most powerful toxins known to man (botulinum toxin is the undisputed leader). The toxin is present in the body at such low doses that it does not trigger an immunological response. Tetanus can therefore be contracted more than once. That is one reason why people with clinical tetanus should still be vaccinated.

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Most cases of tetanus occur after wounds (lacerations, bites, burns, pricks, IM injections, umbilical infections in neonates, infected abortions, a sand flea burrowing under a toenail, infected Guinea worm). Sometimes the focus is a middle-ear infection (otitis media with perforated ear drum). In 20 to 30% of tetanus patients no entry point or wound can be found.