Founded in 1849 as a rural cemetery, Bellefontaine has several architecturally significant monuments and mausoleums such as the Louis Sullivan-designed Wainwright Tomb, which is listed on the National Register of Historic Places.

[citation needed] The cemetery contains the graves of many prominent American pioneers, businesspeople, politicians, and generals who are significant figures in the history of St. Louis and the United States.

Many of the wealthiest families at Bellefontaine have ornate mausoleums which overlook the Mississippi River and have Classical, Romanesque, Gothic, and Egyptian architectural styles.

Within a few months, the Association had hired landscape architect Almerin Hotchkiss, who helped design Green-Wood Cemetery in Brooklyn, to begin drafting and implementing a master plan for Bellefontaine.

Hotchkiss became superintendent of the cemetery for the next 46 years, designed most of Bellefontaine's roadways and landscaping, and oversaw maintenance of the grounds.

Older graves within St. Louis were reinterred to Bellefontaine, including some from the cemetery by the Old Cathedral near the Mississippi River.

With more than 100 acres (40 ha) of open, unused land, the cemetery has room for traditional casketed and vaulted ground burial for 200 years at current rates of usage.