The road is notable for its cross-section of Chicago's northern suburbs, balancing densely developed commercial, industrial, and residential land uses, with open space areas such as forest preserves, parks, golf courses, creeks, rivers, gardens, and Lake Michigan.

Lake Cook Road goes through, or runs adjacent to, sections of the following municipalities from west to east: Algonquin, Barrington Hills, Barrington, Deer Park, Palatine, Long Grove, Arlington Heights, Buffalo Grove, Wheeling, Riverwoods, Northbrook, Deerfield, Highland Park, and Glencoe.

As the road enters the town of Barrington, the road's name changes to Main Street and has an at-grade crossing at the Canadian Pacific Railway, formerly the Elgin, Joliet, and Eastern Railway, and traffic notably increases, particularly in downtown Barrington at the intersections of Illinois Route 59 (Hough Street), U.S. Route 14 (Northwest Highway), and the at-grade Union Pacific/Northwest Line, especially during weekday rush periods, when Metra trains stop frequently at the nearby station.

The road then crosses the Des Plaines River, and goes through the Potawatomi Woods Forest Preserve before entering Riverwoods, Northbrook, and Deerfield.

This area is surrounded by numerous offices, industrial buildings, and corporate headquarters including those of Baxter International, Walgreens, and Underwriters Laboratories.

Lake Cook Road crosses the paths of the four Metra rail lines servicing Chicago's north and northwestern suburbs.

While this makes for very scenic views, it also presents a challenge to the region, as it works to balance environmental preservation with safety, transportation, recreation, and economic development needs.

In addition, near the intersection of Lake Cook Road and the Tri-State Tollway (near Northbrook, Riverwoods, and Deerfield) is a major cluster of office and industrial development which employs thousands of people (known as an edge city), which contains the corporate headquarters for Walgreens, Baxter International, and Underwriters Laboratories, which are all found along the road.

Additional employers can be found within a few miles of the road, extending north–south along Milwaukee Avenue, the Tri-State Tollway, and Skokie Highway.