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The population of Pensacola in 1880 was 6,845.
- February 27 – Daniel F. Sullivan sells majority control of the Pensacola & Louisville Railroad to the Louisville and Nashville Railroad
- September 1 – Pensacola's first Bell telephone comes into operation
- September 15 – The First National Bank opens; Daniel and Martin Sullivan, proprietors
- December 11 – A fire consumes much of Pensacola's downtown business district