I-395 begins as an extension of Hammond Street at an at-grade intersection with US 2 and SR 100 on the south side of Bangor International Airport.

US 2 and SR 100 turn north from the intersection onto Odlin Road, while I-395 reaches a cloverleaf interchange with its parent route, I-95, immediately to the east.

The four-lane freeway is joined by SR 15 and travels east around the south side of Bangor, also becoming concurrent with US 202 near the Beal University campus.

I-395 travels into the rural outskirts of the Bangor area and turns northeastward to terminate at a partial cloverleaf interchange with Wilson Street (part of US 1A) east of Brewer.

The freeway primarily serves as a bypass of Bangor and Brewer for travelers wishing to access the Down East/Bar Harbor region of Maine.

Despite all three affected communities issuing resolutions in 2014 opposing this route,[16] the state went forward with the project as a super two rerouting of SR 9.