Daniel Bissell (portrait left) was born in Connecticut in 1768 and as a youth served in the Connecticut militia as a fifer during the Revolutionary War. In 1788 he enlisted in the U.S. Army and quickly rose through the ranks. In 1802 he was given command of Fort Massac, near Cairo, Illinois, where also served as the port of entry Inspector and Collector. In 1809, as a Lt. Colonel, Bissell was appointed military commander of the Upper Louisiana Territory and took command of the Cantonment Belle Fontaine (later known as Fort Belle Fontaine. This military post was established in 1805 and was the first American military post west of the Mississippi River. It was located in the bottom lands of the Missouri River about five miles west of the confluence with the Mississippi River. Upon his arrival, Bissell found conditions at the fort to be unhealthy and the buildings in poor repair. He also considered the site to be in a poor strategic position. In 1810 Bissell received authorization to relocate the fort on higher ground and completed the rebuilding effort in 1811. The fort was abandoned in 1826 when the army built Jefferson Barracks on a site on the bluffs overlooking the Mississippi River south of St. Louis.

With the onset of the War of 1812, Bissell was promoted colonel and given command of the 5th Infantry and in 1814 he given a brevet promotion to brigadier-general and assigned a brigade in Izard's Right Division at Plattsburgh. He commanded this brigade throughout 1814 and won a tactical draw at the small action fought at Lyon's Creek or Cooks' Mills, Canada, on October 19, 1814. In 1815, after Bissell returned to the St. Louis area from the war, he began to construct a brick house. Using slave labor the house was constructed in stages and was finished by 1819. This oldest portion of the two-story home is a rare example of the Federal style of architecture that was brought to Missouri by American settlers after the Louisiana Purchase.

The placement of the house at the top of a rise and the fine proportions of the Federal Style home made the house a prominent landmark in the sparsely populated area north of St. Louis and east of the village of Florissant. In 1821 General Bissell left the military and retired to his estate which had become known as Franklinville Farms. He became a prosperous farmer by building up the estate to 2300 acres and was a prominent community leader in the early affairs of the St. Louis area. He lived in the house with his wife Deborah and their four children until his death in 1833. The older portion two-story brick house is a rare example of the Federal style of architecture that was brought to Missouri by American settlers after the Louisiana Purchase.

The Bissell House is unusual in that it was occupied by the same family for nearly one hundred and fifty years. Each successive generation made their own alterations and additions. The frame wing was added about 1890 to replace a detached stone kitchen dating back to 1812. In 1933 and 1934, the house received a major overhaul which removed many of the alterations made over the years with the intention of returning the house to its earlier appearance. Remaining evidence of these alterations includes the Classic Revival front doorway and ground floor mantels from the 1840s and the Victorian frame wing from the 1890s, which was added about 1890 to replace a detached stone kitchen dating back to 1812. Numerous outbuildings once dotted the grounds, but none have survived. The home was placed on the National Register of Historic Places in 1978.

In the early 1960s the house and what remained of Franklinville Farms was donated to St. Louis County with the understanding that the property would be used for museum purposes. The house opened as a museum in 1964 and between 1964 and 1970 extensive restoration and landscaping were undertaken and the museum collection enlarged and improved. On display are many original furnishings, historical documents signed by George Washington and Thomas Jefferson and interesting facts about St. Louis life in the 19th century. The Sebor Gallery is located in one wing of the house and features educational and historical exhibits including photographic and video displays. A variety of historical and recreational activities are offered throughout the year including concerts, costumed reenactments, craft fairs, lectures, and seminars.