Final answer:
Smallpox had the highest mortality rate before vaccination became prevalent.
Step-by-step explanation:
The disease that had the highest mortality rate before vaccination became prevalent is Smallpox. Smallpox is caused by the variola major virus and historically had fatality rates of 50% or greater in susceptible populations. It was transmitted through inhalation of viral particles shed from lesions in the throat and spread systemically in the bloodstream, producing a pustular skin rash.