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What is now the St. Cloud area was occupied by various indigenous peoples for thousands of years. Europeans encountered the Ottawa, Ojibwe, and Winnebago when they started to trade with Native American peoples.^{[citation needed]}

Minnesota was organized as a territory in 1849. The St. Cloud area was opened up to settlers in 1851 after treaty negotiations with the Winnebago (Ho-Chunk) tribe in 1851 and 1852. John Wilson, a Maine native with French Huguenot ancestry and an interest in Napoleon, named the settlement St. Cloud after Saint-Cloud, the Paris suburb where Napoleon had his favorite palace.^{[citation needed]}

St. Cloud was a waystation on the Middle and Woods branches of the Red River Trails used by Métis traders between the Canada–US border at Pembina, North Dakota and St. Paul. The cart trains often consisted of hundreds of oxcarts. The Métis, bringing furs to trade for supplies to take back to their rural settlements, would camp west of the city and cross the Mississippi in St. Cloud or just to the north in Sauk Rapids

The City of St. Cloud was incorporated in 1856. It developed from three distinct settlements, known as Upper Town, Middle Town, and Lower Town, that were established by European-American settlers starting in 1853. Remnants of the deep ravines that separated the three are still visible today. Middle Town was settled primarily by Catholic German immigrants and migrants from eastern states, who were recruited to the region by Father Francis Xavier Pierz, a Catholic priest who also ministered as a missionary to Native Americans. Lower Town was founded by settlers from the Northern Tier of New England and the mid-Atlantic states, including former residents of upstate New York.^{[citation needed]}

Upper Town, or Arcadia, was plotted by General Sylvanus Lowry, a slaveholder and trader from Kentucky who brought slaves with him, although Minnesota was organized as a free territory. He served on the territorial Council from 1852 to 1853 and was elected St. Cloud's first mayor in 1856, serving for one year.

Jane Grey Swisshelm, an abolitionist newspaper editor who had migrated from Pittsburgh, repeatedly attacked Lowry in print. At one point Lowry organized a "Committee of Vigilance" that broke into Swisshelm's newspaper office and removed her press, throwing it into the Mississippi River. Lowry started a rival paper, The Union.

The US Supreme Court's 1857 decision in Dred Scott ruled that slaves could not file freedom suits and found the Missouri Compromise unconstitutional, so the territory's prohibition against slavery became unenforceable. Nearly all Southerners left the St. Cloud area when the Civil War broke out, taking their slaves with them. Lowry died in the city in 1865.

Beginning in 1864, Stephen Miller served a two-year term as Minnesota governor, the only citizen of St. Cloud ever to hold the office. Miller was a "Pennsylvania German businessman", lawyer, writer, active abolitionist, and personal friend of Alexander Ramsey. He was on the state's Republican electoral ticket with Abraham Lincoln in 1860.

Steamboats regularly docked at St. Cloud as part of the fur trade and other commerce, although river levels were not reliable. This ended with the construction of the Coon Rapids Dam in 1912–14. Granite quarries have operated in the area since the 1880s, giving St. Cloud its nickname, "The Granite City."

In 1917, Samuel Pandolfo started the Pan Motor Company in St. Cloud. Pandolfo claimed his Pan-Cars would make St. Cloud the new Detroit but the company failed at a time when resources were directed toward the World War I effort. He was later convicted and imprisoned for attempting to defraud investors.

As of the census of 2010, there were 65,842 people, 25,439 households, and 13,348 families residing in the city. The population density was 1,644.4 inhabitants per square mile (634.9/km²). There were 27,338 housing units at an average density of 682.8 per square mile (263.6/km²). The racial makeup of the city was 84.6% White, 7.8% African American, 0.7% Native American, 3.7% Asian, 0.8% from other races, and 2.5% from two or more races. Hispanic or Latino of any race were 2.4% of the population.

There were 25,439 households, of which 25.0% had children under the age of 18 living with them, 37.6% were married couples living together, 10.4% had a female householder with no husband present, 4.5% had a male householder with no wife present, and 47.5% were non-families. 30.8% of all households were made up of individuals, and 7.8% had someone living alone who was 65 years of age or older. The average household size was 2.37 and the average family size was 2.95.

The median age in the city was 28.8 years. 18.9% of residents were under the age of 18; 23.9% were between the ages of 18 and 24; 25.5% were from 25 to 44; 21.5% were from 45 to 64; and 10.3% were 65 years of age or older. The gender makeup of the city was 51.5% male and 48.5% female.

St. Cloud is the principal city of the St. Cloud Metropolitan Statistical Area, a metropolitan area that covers Sherburne, Benton and Stearns counties and had a combined population of 167,392 at the 2000 census.

In the 2000 census, 27.3% of St. Cloud households had children under the age of 18 living with them, 41.4% were married couples living together, 9.4% had a female householder with no husband present, and 45.9% were non-families. 30.2% of all households were made up of individuals, and 8.0% had someone living alone who was 65 years of age or older. The average household size was 2.40 and the average family size was 3.00.

The racial makeup of the city was 91.7% White, 2.4% African American, 0.7% Native American, 3.1% Asian, 0.7% other races, and 1.4% from two or more races. Hispanic or Latino of any race were 1.3% of the population.

The median income for a household in the city was $37,346, and the median income for a family was $50,460. Males had a median income of $33,670 versus $23,759 for females. The per capita income for the city was $19,769. About 5.0% of families and 13.1% of the population were below the poverty line, including 7.0% of those under age 18 and 9.9% of those age 65 or over.