In 1836, the Platte Purchase was made, where the Federal Government "officially” bought 2 million acres of land from the Iowa, Sac, Fox, Sioux and Algonquin Indians for $7,400. After the Platte Purchase, the Indians were moved to a reservation in Northeast Kansas.

The first people to settle in what would soon become Weston were two young soldiers from Fort Leavenworth, Kansas in 1837. Rowing up the Missouri River in a canoe, they discovered that the Missouri River made a natural bay at the foot of what would later become Weston's Main Street. The bay, prime for a steamboat landing or ferry, prompted the young men to purchase property. Selling off a few of their lots, Weston officially began. Joseph Moore, on of the two soldiers, built the first cabin at the corner of what is now Market and Main Streets.

Early settlers arrived from many of the southern states including Kentucky, Tennessee, Louisiana and Virginia, bringing with them the important crops of tobacco and hemp, as well as their southern customs, including slavery. Soon, emigrants from Austria, Germany, Scotland, Ireland, and Switzerland discovered the area, attracted by the rolling hills that reminded them of their homelands. The Platte Purchase allowed these new settlers to homestead their property if they cultivated at least ½ acre and built a dwelling.

In 1838, one of Weston's first entrepreneurs arrived by the name of Ben Holladay, at first establishing a small tavern. Later he would become involved in a number of businesses in the area.

By 1839 Weston had grown to a population of 300. Initially, the main source of income for the settlers was the farming of tobacco. As early as 1840, tobacco was floated on rafts to Glasgow, where it would be packed into hogsheads and shipped on steamboats to St. Louis and Cincinnati.

Tobacco is still cultivated in the Weston area to this day.

Later, the farmers would find that hemp, a product used to make rope, provided an even higher profit, and this became the main cash crop of the time. However, hemp cultivation is very difficult work, requiring the stalks to be combed into fibers. Here, these first southern settlers actively depended upon their southern custom of utilizing slave labor for the work.