Seventh cranial nerve (facial nerve) passes through a portion of temporal bone known as the facial canal. Inflammation of at the part of the nerve termed geniculate ganglion (a group of fibers and sensory neurons) leads to compression within this bony canal.

This can in turn block the transmission of neural signals, result in ischemia and demyelination, and cause facial paralysis or Bell's palsy. Injury is peripheral to the facial nerve's nucleus, and such compression has been proven on MRI scans (magnetic resonance imaging).

Bell's palsy is considered an idiopathic condition, which means the cause of the inflammation is not known and the exact pathophysiology remains uncertain. Several viruses are associated with this disease, and herpes simplex virus type 1 (HSV-1) is thought to be the most probable causative factor, as affected individuals have elevated antibody titers for this virus. Other infectious agents may play a role in certain cases, such as Epstein-Barr virus and cytomegalovirus (which both cause infectious mononucleosis), adenovirus, mumps and rubella. Bilateral facial palsy has also been linked to acute HIV-infection.

The hypothesis that HSV-1 is the etiologic agent in Bell's palsy was proposed in 1972 by McCormick. After causing primary infection in the form of cold sores (clusters of small fluid-filled blisters on the lips, mouth or nose), the virus travels along the neuron (in a process called retrograde transport) to the geniculate ganglion. There a lifelong silent infection is established, and autopsy studies showed the presence of HSV-1 in the ganglions of affected patients. The virus can be reactivated when the immune defenses are low, causing local damage to the nerve.

Other conditions can also produce isolated facial nerve palsy that can be hard to distinguish from Bell's palsy, however their pathophysiological background is different. Pathological structures in the ear or parotid gland, such as cholesteatoma or salivary tumors, can result in facial nerve compression and subsequent paralysis. Ramsay-Hunt syndrome is characterized by an outbreak of herpes zoster in the facial nerve distribution and can present with an indistinguishable clinical picture. Guillain-Barré syndrome, an acute polyneuropathy affecting the peripheral nervous system, can also result in similar facial weakness. Lyme disease, sarcoidosis, otitis media and reaction to influenza vaccine are other causes of peripheral nerve palsies. All of them usually present with additional features that sets them apart from Bell's palsy.

In approximately 4% of cases this condition can be linked to a family history. The inheritance in such cases is thought to be autosomal dominant with low penetrance, which means that merely a fraction of those who inherit the mutation actually develop the disease, despite the fact that only one mutated copy of the gene is needed. Still, the specific predisposing factors that are inherited are still unclear. In hereditary cases family history may also be positive for other nerve disorders or neurologic deficits. A rare form of familial Bell's palsy that has a propensity for young women also exists.