The highway serves as an easterly bypass of the Toledo metropolitan area, passing through the communities of Northwood and Oregon.

The southern end of I-280 is an interchange in Wood County with exit  71 along the Ohio Turnpike, which carries I-80 and I-90 at this point.

The Interstate crosses the river on the Veterans' Glass City Skyway, an 8,800-foot (2,700 m), cable-stayed bridge.

The removal of direct access to Hanley and Latcha was originally disputed by business owners who owned motels and gas stations along those roads.

[10] Originally, I-280 was carried across the Maumee River by the Robert Craig Memorial Bridge, a drawbridge that frequently caused backups along the route.

In addition, a ramp leading from northbound Summit Street to southbound I-280 merged directly onto the bridge with no acceleration room, so it was removed in the mid-1990s.