The area found itself frequently caught between warring factions, including American Indian and European interests.

By 1797, a young surveyor from Virginia named Lucas Sullivant had founded a permanent settlement on the west bank of the forks of the Scioto River and Olentangy River.

An admirer of Benjamin Franklin, Sullivant chose to name his frontier village "Franklinton".

It is Ohio's third largest metropolitan area, behind Cleveland and Cincinnati. Census Bureau, the Columbus-Marion-Zanesville, OH Combined Statistical Area (which also includes Marion, Chillicothe, and Mount Vernon) has a population of 2,424,831, making it the second largest metropolitan area in Ohio behind Cleveland.

Under the Combined Statistical Area (CSA) model, the Columbus, OH Metropolitan Statistical Area was the 25th largest in the United States. The city proper has also expanded and annexed portions of adjoining Delaware County and Fairfield County.

During this period the region routinely suffered turmoil, massacres and battles.

The 1763 Treaty of Paris ceded the Ohio Country to the British Empire.

A large Irish population settled in the north along Naghten Street (presently Nationwide Boulevard), while the Germans took advantage of the cheap land to the south, creating a community that came to be known as the Das Alte Südende (The Old South End).

Columbus's German population constructed numerous breweries, Trinity Lutheran Seminary, and Capital University.

Over 2,000 Confederate soldiers remain buried at the site, making it one of the North's largest Confederate cemeteries. By virtue of the Morrill Land-Grant Colleges Act, the Ohio Agricultural and Mechanical College (which became The Ohio State University) founded in 1870 on the former estate of William and Hannah Neil. By the end of the 19th century, Columbus was home to several major manufacturing businesses.