SR 161 heads northwest along Boundary Line Road, then Main Street through the center of Fort Fairfield.

The road curves to the west, intersects SR 205 at its northern terminus, crosses the Aroostook River, and enters the city of Caribou.

The four-lane highway has a few intersections with local roads before becoming divided and has another state route, SR 89, joins the roadway for about 1⁄2 mile (0.80 km).

The road passes directly in front of the U.S. Customs station at the Fort Kent–Clair Border Crossing.

Now closely paralleling the St. Johns River, Main Street continues past more houses before the surroundings become more rural.

It ascends the side of a small hill away from the river but later descends towards the town center of Allagash.

In order to promote downtown development and reroute through heavy traffic, the Caribou Connector was proposed.

After marking a few curves and crossing over Caribou Stream, the two routes split into a one-way pair through the downtown business district.

Northbound SR 161B continues north along Main Street while the southbound travels along Hatch Drive.

The northbound route heads north from this point and intersects SR 89 at its western terminus (High Street).

SR 161B north turns to the west on Herschel Street passing numerous businesses.

After making passing many businesses, the road heads south along Prospect Street for one block before rejoining the southbound side of the route.

It passes many houses, businesses, and Caribou High School before reaching the eastern terminus of SR 228.

Continuing northwest, SR 161B and Sweden Street pass more houses but some farmland begins to line the road.