The Menominee Nation ceded the territory to the United States in the Treaty of the Cedars in 1836.

[13] The first European settlers in Appleton were fur traders seeking to do business with Fox River Valley Native Americans.

Hippolyte Grignon built the White Heron in 1835 to house his family and serve as an inn and trading post.

Samuel Appleton, Lawrence's father-in-law from New England who never visited Wisconsin, donated $10,000 to the newly founded college library, and the town took his name in appreciation.

In order to provide electricity to the paper industry, the nation's first hydro-electric central station, the Vulcan Street Plant on the Fox River, began operation on September 30, 1882.

[18] Shortly thereafter, in August 1886, Appleton was the site for another national first, the operation of a commercially successful electric streetcar company.

Appleton also had the first telephone in Wisconsin, and the first incandescent light in any city outside of the East Coast.

Significant annexations to the city, taken from the Town of Grand Chute, were performed in the next two decades.

[21] Another became official on December 22, 1950, after multi-year disputes, when the unincorporated villages of Bell Heights and Whispering Pines were annexed into the city from Grand Chute.

From approximately 1930–1970, Appleton was a sundown town: black people were not allowed to stay overnight,[24] and none lived within its city limits by 1930.

[25] In 1936, the Institute of Paper Chemistry tried to hire the famous African-American chemist Percy Julian, but could not figure out how to do this without running afoul of what was stated as "an arcane law on the City of Appleton's books".

[27][26] Appleton's sundown status was largely de facto and not de jure; it stood by unwritten consensus and enforcement, such as by police strongly encouraging black people to leave town after dark.

[28] Following the Flint water crisis, a report of Wisconsin Rust Belt cities showed high levels of lead contamination in the water of Appleton, with children under the age of 1 testing positive for lead.

This is tied for the second highest dew point ever observed in the United States and coincides with the 1995 Chicago heat wave.

[31] Appleton is the principal city of the Appleton–Oshkosh–Neenah CSA, a Combined Statistical Area which includes the Appleton (Calumet and Outagamie counties) and Oshkosh–Neenah (Winnebago County) metropolitan areas,[citation needed] which had a combined population of 392,660 at the 2010 census[34] and an estimated population of 409,881 as of 2019.

The Atlas Science Center has historic paper-making machines on display and an exhibit on the history of paper.

In 2013, Houdini Plaza, on the corner of College Avenue and Appleton Street, was renovated.

The park's facilities include: seven baseball/softball fields, playground equipment, an indoor ice skating rink, a sledding hill, a picnic pavilion, a catch-and-release fishing pond, grills, and a warming shelter.

[49] The park provides a firework display for the Appleton community during the 4th of July holiday.

Jones Park is the site of the finish line for the Santa Scamper run held during the annual Appleton Christmas Parade, and features an outdoor hockey rink in the winter.

The current mayor of Appleton, Jake Woodford, was elected in 2020 to his first four-year term.

[57] In recent years, Appleton has emerged as a center for innovation in technology education, particularly in the area of K–12 technology education: the student-driven Appleton Youth Education Initiative has partnered with Microsoft Philanthropies, Plexus Corp., Miron Construction, Schneider National, and Stellar Blue Technologies to organize the Appleton Tech Clinic and HackAppleton, a popular annual hackathon that draws students from all over Wisconsin.

Amtrak Thruway and Lamers Bus Lines offer intercity buses serving such locations as Green Bay, Madison, Oshkosh, Fond du Lac, Milwaukee, and Chicago.

[citation needed] In April 2021, Bird Rides launched a pilot program with 100 rentable electric scooters that users can operate throughout most of the city.

[67] Roads include: Appleton is crisscrossed by the former main lines of the Chicago and North Western Railway (southwest-northeast) and the Milwaukee, Lake Shore and Western Railway (roughly southeast–northwest, and now largely abandoned except for local service to area paper mills and other industries).

A north-south branch of the former Wisconsin Central Railroad passes on the west side of the city.