It runs through the city of Minneapolis before rejoining with I-35E to reform I-35 in Columbus near Forest Lake.

In the case of I-35 in the Twin Cities area, since neither branch is clearly the main route and both branches return to a unified Interstate beyond the cities of Minneapolis and Saint Paul, officials at the American Association of State Highway and Transportation Officials (AASHTO) have allowed the suffixes of E and W in Minnesota to remain in the present day.

While I-35E takes a northeasterly path into Saint Paul, I-35W heads north into Minneapolis.

I-35W continues northbound into Richfield, where it turns east and joins with Minnesota State Highway 62 (MN 62) for about 0.25 miles (0.40 km) in what is locally known as the Crosstown Commons.

I-35W swerves slightly northeast immediately south of downtown to avoid the Washburn-Fair Oaks Mansion District.

Here, I-35W passes through industrial areas near the suburbs of St. Anthony, Lauderdale, Roseville, and Arden Hills.

I-35W and US 10 run concurrently for another one mile (1.6 km) before the latter turns westward in Mounds View and Shoreview at exit 30.

I-35W passes next to the former site of the Twin Cities Ordnance Plant and again turns northeastward through the suburbs of Blaine and Lino Lakes.

I-35W is prone to heavy-rain event flooding in several areas, intersecting both natural habitats, including the Minnesota Valley National Wildlife Refuge between Burnsville and Bloomington, and the dense urban areas through the city of Minneapolis.

[5] The storm sewer system under I-35W in the urban core of south Minneapolis has also been cited as a place prone to flashfloods during rain events.

Improvements were made in 1984 to redeck and widen the bridge, but subsoil problems found at the north end resulted in the new lanes being temporarily closed.

[11][12][13] Because of the collapse of the bridge, I-35W traffic was temporarily detoured through eastbound I-94 to northbound MN 280 where it meets up with I-35W in Roseville.

The replacement I-35W Saint Anthony Falls Bridge was built in less than a year and opened to traffic on September 18, 2008, at 5:00 am CDT, three months ahead of schedule.

[22] The METRO Orange Line bus rapid transitway runs from the southern suburb of Burnsville to downtown Minneapolis on I-35W, passing through Bloomington, and Richfield.