Most of the town was destroyed in April 1881 by flooding, as the Mississippi River shifted eastward to a new channel, taking over the lower 10 mi (16 km) of the Kaskaskia River. This resulted from deforestation of the river banks during the 19th century, due to crews taking wood for fuel to feed the steamboat and railroad traffic. The river now passes east rather than west of the town. The state boundary line, however, remained in its original location. Accordingly, if the Mississippi River is considered to be a break in physical continuity, Kaskaskia is an exclave of Illinois, lying west of the Mississippi and accessible only from Missouri. A small bridge crosses the old riverbed, now a creek that is sometimes filled with water during flood season. Kaskaskia has an Illinois telephone area code (618) and a Missouri ZIP Code (63673). Its roads are maintained by Illinois Dept. of Transportation, and its few residents vote in the Illinois elections. The town was evacuated in the Great Flood of 1993, which covered it with water more than nine feet deep.
The site of Kaskaskia near the river was first a Native American village, inhabited by varying indigenous peoples for thousands of years. The historic Illini peoples lived in this area at the time of European encounter and traded with the French colonists.
French colonists named the town after the Illini word for the Kaskaskia River but, historically, it was referred to as Kasklas, Kaskasky, Cas-caskias, Kasquskias, and Kaskaskias, with many spelling variations. In 1703, French Jesuit missionaries established a mission with the goal of converting the Illini Native Americans to Catholicism. The congregation built its first stone church in 1714. The French also had a fur trading post in the village. Canadien settlers moved in to farm and to exploit the lead mines on the Missouri side of the river.
Favorably situated on a peninsula on the east side of the Mississippi River, Kaskaskia became the capital of Upper Louisiana and the French built Fort de Chartres nearby in 1718. In the same year they imported the first enslaved Africans, shipped from Santo Domingo in the Caribbean, to work as laborers in the lead mines being developed in Missouri.
From the years of early French settlement, Kaskaskia was a multicultural village, consisting of a few French men and numerous Illinois and other American Indians. In 1707, the population of the community was estimated at 2,200, the majority of them Illinois who lived somewhat apart from the Europeans. Writing of Kaskaskia about 1715, a visitor said that the village consisted of 400 Illinois men, "good people;" two Jesuit missionaries, and "about twenty French voyageurs who have settled there and married Indian women." Of 21 children whose birth and baptism was recorded in Kaskaskia before 1714, 18 had mothers who were Indian and 20 had fathers who were French. One devout Catholic full-blooded Indian woman disowned her mixed-race son for living "among the savage nations," as she referred to the French.