The extension of the Midwestern section of I-88 from the Chicago area to Binghamton would follow approximately this routing:
- I-290 between I-294 and I-90/94
- I-90/94 between I-290 and the I-90/94 split on the south side of Chicago
- I-90 between the I-90/94 split on the south side of Chicago and I-65 in Northwest Indiana
- I-65 between I-90 (Indiana Toll Road) and Merrillville, IN
- Merrillville, IN and Canton, OH along US 30 (including the existing freeway segments of US 30 in Ohio)
- US 62 between Canton, OH and I-80 in the Youngstown, OH area
- I-80 between Youngstown, OH and Mercer, PA
- US 62 between Mercer, PA and Warren, PA
- A new section of highway between Warren, PA and Steamburg, NY
- I-86 between Steamburg, NY and Binghamton, NY
The extension of the Midwestern section of I-88 between the Quad Cities and Downtown Kansas City, MO would follow the routing of the Chicago-Kansas City Expressway.
The section of I-88 in Upstate New York could also be extended further east from the I-88/I-90 interchange in Rotterdam, NY to I-95 in Portsmouth, NH.