Officials have not yet determined why Patience charged elephant manager John Phillips Bradford, 62, who had worked at the zoo for 30 years.
However, there were reports that the female elephant had a history of aggressive behavior.
"This is very sad day for the zoo family, as well as our community as a whole," said Mike Crocker, director of the Dikerson Park Zoo in Springfield, Missouri.
Several other staff were on hand with Bradford when the elephant charged at 8:45 am.
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"We haven't had a situation like this happen before."
Zoo officials were forced to euthanize the herd's matriarch, Connie, last week after she lost nearly 1,000 pounds due to advanced kidney disease and then simply lay down and was unable to get up.
It was not clear what would happen to Patience, but the zoo said it would remain open on Friday.
Patience, 41, has been at the zoo since 1990, the Springfield News-Leader reported. The zoo's elephant herd consisted of three females and two males prior to Connie's death.