The Lewis and Clark Expedition stopped at "Bear Medison" island, near the location of today's city hall.

Another suggested theory of origin is related to a story about a discharged US Army dragoon by the name of Joseph Moore.

He bought the land and then had First Sergeant Tom Weston of D Company, First Dragoons, stationed at Fort Leavenworth across the Missouri River, lay out a town plan.

In 1881, Weston was the site of the lynching of the biracial Charles Reese after he was accused of the rape and murder of the sixteen-year-old Nancy Stillwell.

[7] The Weston Brewing Company was first established in 1842 by German immigrant John Georgian, and was one of the first lager beer breweries in the U.S. Five arched, limestone cellars, dug to a depth of 55 feet below ground, were constructed to create the ideal conditions for Georgian's lager beer, which needed to be stored below 60 degrees.

[8] The McCormick Distillery, Missouri District Warehouse, Pleasant Ridge United Baptist Church, Sugar Creek Site, and Weston Historic District are listed on the National Register of Historic Places.

[9][10] According to the United States Census Bureau, the city has a total area of 3.35 square miles (8.68 km2), all land.

Weston is the home of McCormick Distilling Company, producers of a large number of liquors, it was founded in 1856, and is the oldest whiskey distillery west of the Mississippi River and the oldest continuously operated distillery in the United States.

Weston was, prior to its cultivation being prohibited by the 1937 Marihuana Tax Act, the world's leading producer of industrial hemp.

Today about 2.8 million pounds of tobacco is grown annually in Platte County.