[4] The county was developed for agriculture and the timber industry, with products such as turpentine, lumber, and plywood.

In November 1858 a railroad was completed connecting Jacksonville to Alligator, which opened the town to more commerce and passenger traffic.

[6] During the American Civil War, the railroad between Lake City and Jacksonville was used to send beef and salt to Confederate soldiers.

[7] Confederate General Joseph Finnegan assembled troops and called for reinforcements from P. G. T. Beauregard in response to the Union threat.

On February 11, 1864, Finnegan's troops defeated a Union cavalry raid in Lake City.

[7] After the Union cavalry was repulsed, Finnegan moved his forces to Olustee Station about ten miles east of Lake City (in Baker County).

The Confederate presence at Olustee Station was reinforced to prepare for the Union troops coming from Jacksonville.

Whites lynched 20 African Americans in Columbia County from 1877 to 1950, mostly in the decades near the turn of the 20th century.

[10] Among these murders was the mass lynching on May 21, 1911, of six black men who were taken from the jail by a white mob in Lake City.

Columbia County is coterminous with the Lake City, Florida Micropolitan Statistical Area (μSA).

According to the Secretary of State's office, Republicans are the majority of registered voters in Columbia County.

Until 1971, Lake City was a stop on the Louisville and Nashville and Seaboard Coast Line's Gulf Wind (New Orleans - Jacksonville).

The Seaboard Air Line operated this and another passenger train in each direction through Lake City until 1966 or 1967.

[29] Another one is owned by the Georgia Southern and Florida Railway, and runs along US 41 from Lake City through Hamilton County.