On August 24, 1804, Lewis & Clark camped near the Vermillion River and visited Spirit Mound the next day.

While fur trappers and trading posts were the first European American presence to set up permanent residence it wouldn’t be until access improved with steamboats, military road, and Native Americans were forced onto reservations that settlers would arrive in 1859. Vermillion however would have several stops and starts as things got sort of biblical with floods and fires. The railroad came through in the 1870s and Vermillion incorporated and officially was off and growing below the bluff along the Missouri River.

The snowy winter of 1880 would create an ice jam in 1881 as everything melted which resulted in a huge flood that almost wiped Vermillion off the map. A few buildings would be salvaged and moved to the bluff where the city would be rebuilt. In 1883 a fire would ravage the city and again in 1890 which caused the city to have an ordinance that buildings must be made out of fireproof materials.

Part of the success of Vermillion comes from the fact they were picked by the first legislature of Dakota Territory in 1862 to establish a University however first classes would not be held until 1883 with the iconic Old Main building by Sioux Falls architect Wallace Dow. The University of South Dakota continues to be a lifeblood for Vermillion.

Today the city has also invested in preserving its historical sites, with efforts to maintain and celebrate its unique past. Visitors and residents alike appreciate the balance of small-town friendliness with the amenities and opportunities that come with being a university town.

The spirit of resilience that has defined Vermillion throughout its history continues to guide its future, as it embraces growth and change while honoring the legacy of those who built and rebuilt it. Whether it's through education, the arts, or community engagement, Vermillion stands as a testament to the enduring power of perseverance and community.