The Saint George originated in 1845 as a three-story structure with 47 rooms on the top two floors. Billed as a working man's hotel, the first floor provided a saloon, sample rooms, a lobby-tobacco shop, a restaurant, and two retail spaces. Weston quickly became known as a port town, where traveling salesmen took respite from the mighty river to set up temporary "sample" shops behind the saloon in The Saint George hotel where they sold their wares. A fire in 1890 left the building in ruins with only the two street side brick walls left standing. Completed in 1891, the rebuilt structure was ten feet shorter than the original. Except for the time between the fire and the reconstruction, the hotel was open continuously until 1984 when another fire ended occupancy.

In the early 1800's, the Missouri River flowed briskly past its banks to a town which was established only eight years prior to the building of The Saint George hotel. The river mightily flowed, bringing with it steamboat captains and travelers from all walks of life. Weston, Missouri, established in 1837, became a boom town in those days and was one of the two largest ports on the Missouri River, second only to St. Louis, Missouri. The pathway of the river played a major role in this great boom. It was the last place wagon trains could stock up before they crossed the Missouri River and entered wilderness. The steamboats unloaded supplies for Fort Leavenworth and supplies for Westward travelers, and then loaded back up with Weston products of tobacco, hemp ropes, hides, and later lumber, whiskey, and fruit as they headed home. The population in Weston soared to about 5,000 in those days, surpassing both Kansas City and St. Joseph.

Weston enjoyed its prosperity for many years. However, the flood of 1858 crippled the steamboat trade for months and destroyed the port to Weston. The Civil War tore Weston apart, dividing its residents. By 1870 the population was only 900 people. In 1881 the fickle river flooded and slipped into an old channel 2 miles west of Weston, taking the steamboats with it. Still, Weston persevered for the past 167 years, and is once again bustling.