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Noblesville's history dates to 1818 when the government purchased the land which is now Hamilton County from the Native Americans in this area. William Conner, the only settler living in the area at the time, and his wife Mekinges Conner, a Lenape woman, established the first trading post in central Indiana in 1802 and lived in the area's first log cabin. William Conner and Josiah Polk laid out what is now downtown Noblesville in 1823, which was designated as the Hamilton County seat in 1824 and incorporated in 1851. Conner's 1823 home is now one of a village of historic buildings that make up Conner Prairie Pioneer Settlement, a living history museum south of Noblesville in Fishers.

Noblesville was named either for James Noble, one of the first two US senators from Indiana, or, according to legend, for Lavina Noble of Indianapolis, to whom Josiah Polk was engaged.

The Peru and Indianapolis Railroad was completed through town in 1851, strengthening the town economically and causing the population to increase. In 1875 work began on the town's second railroad, the Anderson, Lebanon and St. Louis, later known as the Midland.^:122

The city's first large growth period occurred during the Indiana gas boom, with the discovery in 1888 of Noblesville's first natural gas well near 11th and Pleasant streets. Many Victorian homes, as well as most of the downtown commercial district, were built during this time of prosperity. The city has undergone another increase recently as its population grew from 28,590 in 2000 to 51,969 in 2010. This growth echoes the increase in population of much of southern Hamilton County due to its proximity to Indianapolis.

Noblesville was once noted for its flour mills, the mostly widely known of which was the Noblesville Milling Company, producer of Diadem and Kismet flours. In 1925, the manager of the company offered to buy uniforms for the local high school athletic team in exchange for the school adopting the nickname "Millers". The nickname persists to this day.

Other prominent businesses included the Union Sanitary Manufacturing Company, the American Strawboard Company and Firestone Industrial Products.

Among the notable disasters that have struck the town are the Great Flood of 1913, an interurban wreck on the courthouse square in 1919,^:126 and the Goeke fire of 1967. The fire, which began at the Paul Goeke auto dealership just off the square, destroyed two buildings and killed a firefighter'.

The old Hamilton County Sheriff's Residence and Jail on the southwest corner of the courthouse square in downtown Noblesville is now the home of the Hamilton County Museum of History. As a working jail, it once housed Charles Manson as a teenager and D. C. Stephenson, former Grand Dragon of the Indiana Ku Klux Klan. The Stephenson trial, which took place in the adjoining Hamilton County courthouse in 1925, broke the power of the Klan in Indiana and drew national attention to Noblesville. Stephenson was convicted of second-degree murder in the death of Madge Oberholtzer.

During the early 1920s, Noblesville was one of several Indiana towns where the Ku Klux Klan was active, but the Klan's influence quickly faded after Stephenson's conviction. In 1973 Klansmen staging a march in Noblesville were met by counter-demonstrators carrying anti-Klan placards.

In 1995, a local contractor stumbled across a trunk containing Klan paraphernalia and membership records from the 1920s. The debate over how to handle the sensitive issue again put Noblesville in the national spotlight. The Hamilton County Historical Society, which received donated materials, opted to keep the public from seeing the former members' names.

Noblesville also attracted national media attention in 1965 when Noblesville Daily Ledger editor James T. Neal was charged with contempt by Hamilton County Circuit Court judge Ed New. Neal's fight for the First Amendment went before the Indiana Supreme Court. In May 2018, it drew national attention again as the Noblesville West Middle School was the site of a school shooting with a teacher and student injured.

As of 2000, the median income for a household in the city was $73,395, and the median per capita income was $33,732. Approximately 45.22% of the population has a higher education degree with over 87.3% of the population at least having a high school diploma or GED. The median housing value is $171,272 with a total of 17,915 housing units.

As of the census of 2010, there were 51,969 people, 19,080 households, and 13,989 families residing in the city. The population density was 1,656.6 inhabitants per square mile (639.6/km²). There were 21,121 housing units at an average density of 673.3 per square mile (260.0/km²). The racial makeup of the city was 91.1% White, 3.6% African American, 0.2% Native American, 1.7% Asian, 0.1% Pacific Islander, 1.6% from other races, and 1.8% from two or more races. Hispanic or Latino of any race were 4.3% of the population.

There were 19,080 households, of which 42.9% had children under the age of 18 living with them, 58.3% were married couples living together, 10.8% had a female householder with no husband present, 4.2% had a male householder with no wife present, and 26.7% were non-families. 21.6% of all households were made up of individuals, and 6% had someone living alone who was 65 years of age or older. The average household size was 2.69 and the average family size was 3.15.

The median age in the city was 33 years. 30.2% of residents were under the age of 18; 6.5% were between the ages of 18 and 24; 33% were from 25 to 44; 21.6% were from 45 to 64; and 8.7% were 65 years of age or older. The gender makeup of the city was 48.4% male and 51.6% female.