From west to east, it runs from an interchange with Interstate 90 (I-90) and I-94, also known as the Kennedy Expressway, to U.S. Route 41 (US 41), also known as Lake Shore Drive, just west of Lake Michigan.

Ohio Street begins at an interchange with the Kennedy Expressway (I-90/I-94) in the northwestern portion of downtown Chicago.

It then passes under Milwaukee Avenue and Halsted Street before crossing the North Branch of the Chicago River.

At its intersection with McClurg Court, the building 400 East Ohio Street stands 505 feet (154 m) tall with 50 floors.

Ohio Street finally intersects US 41, its eastern terminus also known as Lake Shore Drive.