In the mid-18th century, the area was inhabited by the Potawatomi, a Native American tribe who had succeeded the Miami and Sauk and Fox peoples in this region. The Potawatomi are part of a long-term alliance, called the Council of Three Fires, with the Ojibway and Odawa. In the Council of Three Fires, the Potawatomi are considered the "youngest brother" and are referred to as Bodwéwadmi, a name that means "keepers of the fire." The Potawatomi were forcibly removed from their land after the Treaty of Chicago in 1833 and sent west of the Mississippi River during Indian Removal.

The first known non-indigenous permanent settler was trader Jean Baptiste Point du Sable. Of African descent and possibly born in the French colony of Saint-Domingue (Haiti), Du Sable established a settlement in the 1780s, married a Native American woman, Kitiwaha, and had two children. He is commonly known as the "Founder of Chicago".

As the first major U.S. airport planned after World War II, O'Hare's innovative design pioneered concepts such as concourses, direct highway access to the terminal, jet bridges, and underground refueling systems. Named after Edward "Butch" O'Hare, the U.S. Navy's first WWII Medal of Honor recipient, it routinely ranks among the world's busiest airports.

Chicago's motto, urbs in horto or "city in a garden", was adopted in the 1830s and alludes to the city's impressive and historic park system.

Bertha Palmer was a prominent Chicago socialite whose husband owned the Palmer House Hotel. In 1893, she asked the hotel's pastry chef for a dessert suitable for ladies attending the Chicago World's Columbian Exposition. She requested a cake-like confection smaller than a piece of cake that could be included in boxed lunches. The result was the Palmer House Brownie with walnuts and an apricot glaze. The Palmer House Hotel serves a dessert to patrons made from the same recipe to this day.

House music was created in the 1980s when DJs and music producers from Chicago's underground club culture began altering disco songs to give them a more mechanical beat and deeper bassline. The genre went on to become a worldwide phenomenon and was eventually incorporated by major pop artists including Janet Jackson, Madonna, and Kylie Minogue.

The river is dyed a bright shade of emerald green every year for St. Patrick's Day. Once it's dyed, the river stays green for around 24 to 48 hours.

The Chicago Board of Trade listed the first-ever standardized 'exchange traded' forward contracts in 1864, which were called futures contracts. This contract was based on grain trading, and started a trend that saw contracts created on a number of different commodities as well as a number of futures exchanges set up in countries around the world.

The earliest known softball game was played in Chicago, Illinois on Thanksgiving Day, 1887. It took place at the Farragut Boat Club at a gathering to hear the outcome of the Yale University and Harvard University football game. When the score was announced, a Yale alumnus threw a boxing glove at a Harvard supporter. The Harvard fan grabbed a stick and swung at the rolled up glove. George Hancock, a reporter covering the event, called out "Play ball!" and the game began. This first contest ended with a score of 41-40. The ball, being soft, was fielded barehanded.

Chicago is the county seat of Cook County, the second most populous county in the U.S.