Skokie was originally a German-Luxembourger farming community, but was later settled by a sizeable Jewish population, especially after World War II.

During the real estate boom of the 1920s, large parcels were subdivided; many two- and three-flat apartment buildings were built, with the "Chicago"-style bungalow a dominant architectural specimen.

During the night of November 27–28, 1934, after a gunfight in nearby Barrington that left two FBI agents dead, two accomplices of notorious 25-year-old bank-robber Baby Face Nelson (Lester Gillis) dumped his bullet-riddled body in a ditch along Niles Center Road adjoining the St. Peter Catholic Cemetery,[12] a block north of Oakton Street in the town.

[13] The first African-American family to move to Skokie arrived in 1961, and open-housing activists helped to integrate the suburb subsequently.

Solid Waste Agency of Northern Cook County (SWANCC) v. U.S. Army Corps of Engineers, 531 U.S. 159 (2001) touched upon the Commerce Clause.

In 1977 and 1978, Illinois neo-Nazis of the National Socialist Party of America (NSPA) attempted to hold a march in Skokie, far from their headquarters on Chicago's south side.

The park is located in what was then a predominantly all-white neighborhood, similar to the situation in 1966, when a crowd of 4,000 Marquette Park residents gathered to watch Martin Luther King Jr. lead a march, some waving Confederate flags or throwing bottles, bricks and rocks at the protesters; King was knocked to his knees when struck by a rock.

Given the many Holocaust survivors living in Skokie, the village's government thought the Nazi march would be disruptive, and refused the NSPA permission to hold the event.

The NSPA appealed that decision, and the American Civil Liberties Union interceded on their behalf, in National Socialist Party of America v. Village of Skokie.

Ultimately, the case went all the way to the United States Supreme Court, and resulted in an overturn of the federal migratory bird rule.

Besides strong manufacturing and retail commerce bases, Skokie's economy will add health sciences jobs; in 2003, Forest City Enterprises announced their re-development of the vacant Pfizer research laboratories, in downtown Skokie, as the Illinois Science + Technology Park, a 23-acre (93,000 m2) campus of research installations—2 million square feet (190,000 m2) of chemistry, genomics, toxicology laboratories, clean rooms, NMR suites, conference rooms, etc.).

In 2006, NorthShore University HealthSystem announced installing their consolidated data center operations at the park, adding 500 jobs to the economy.

More recently, the village has focused heavily on the revitalization of both the downtown and central business districts, incorporating Transit Oriented Development principles in the process.

[32] The Skokie Northshore Sculpture Park is situated along the North Shore Channel between Dempster Street and Touhy Avenue on the east side of McCormick Boulevard.

[34] In addition to municipally-managed public spaces, the village is also home to the North Shore Center for the Performing Arts, encompassing Centre East, Northlight Theatre and the Skokie Valley Symphony Orchestra.

[38] The Skokie Park District maintains public spaces and historical sites within its more than 240 acres (0.97 km2) of parkland and in its ten facilities.

[40][41] In 2023, the Village announced plans to extend the Valley Line Trail from its current terminus at Dempster-Skokie Station to its northernmost boundary at Old Orchard Road.

Jewish: Muslim: Roman Catholic: The Chicago "L"s Yellow Line terminates at the Dempster Street station in Skokie.

[48] Additionally, the CTA is commissioning an alternatives analysis study on the extension of the Yellow Line terminal to Old Orchard Road for Federal Transit Administration New Start grants.

[49] The New Starts program allows federal funds to be used for capital projects provided that all extensions for a given problem (i.e., enabling easy transportation for reverse commuters to Westfield Old Orchard) are considered.

For automobile transport, Interstate 94, the Edens Expressway, traverses western Skokie, with interchanges at Touhy Avenue, Dempster Street, and Old Orchard Road.

An image of Oakton Street in Skokie portrayed the fictional town of Mayfield in television show Leave it to Beaver.