Only about a 1⁄2 mile (0.80 km) of its length is in Pennsylvania; the Milford–Montague Toll Bridge carries it over the Delaware River into New Jersey, where it connects to the remainder of the route.

The highway's northern terminus is at an intersection of US 209 near Milford, Pennsylvania; some sources and signs show an overlap with US 209 to end at its parent route US 6.

The route connects several cities and towns, including Bordentown, Trenton, Princeton, Somerville, Roxbury, Netcong, and Newton.

US 206 begins at the intersection of White Horse Pike (US 30) in Hammonton in Atlantic County, heading north-northeast on the two-lane, undivided highway.

[1][3] In Shamong Township, the road makes a turn to the north and crosses an abandoned railroad line before it passes by Atsion Lake.

[1] Following the intersection of Medford Lakes Road (CR 532), residential development increases along the route as it continues into Southampton.

It becomes a divided highway again and merges with the northern terminus of Route 68, the main access road to the Fort Dix entity of Joint Base McGuire-Dix-Lakehurst, at a directional intersection.

[1] Past US 130, US 206 crosses under Conrail Shared Assets Operations' Robbinsville Industrial Track railroad line and heads through development as a four-lane divided highway, making a slight northwest bend before resuming north.

As the road heads toward downtown Trenton, it crosses NJ Transit's River Line immediately before interchanging with Route 129.

From here, the road turns more to the northwest with four lanes and passes by the CURE Insurance Arena before crossing over Amtrak's Northeast Corridor railroad line and US 1 without an interchange simultaneously.

[1] At this point, both directions of US 206 are in Lawrence and rejoin, with US 206 continuing north as a two-lane undivided road and CR 583 heading to the northeast.

Bayard Lane carries the route past more wooded developed areas, eventually curving northeast through a park.

[1] In Montgomery Township, the route runs to the east of Princeton Airport and crosses the intersection of Georgetown-Franklin Turnpike/Washington Street (CR 518).

Following this intersection, CR 533 splits from US 206 by heading northeast on Bridgepoint Road, and US 206 continues north-northwest through a mix of suburban and rural areas.

[1][3] In this area, US 206 passes over CSX's Trenton Subdivision railroad line before making a turn to the northeast and then to the north, narrowing back to two lanes.

[3] Leaving the center of Hillsborough, the road runs northeast past more wooded areas as it crosses under Norfolk Southern's Lehigh Line.

[3] As US 206 reaches an intersection of Flanders-Bartley Road (CR 613), the surroundings becomes commercial before the route passes under Dover and Rockaway River Railroad's High Bridge Branch.

[1][3] Business in the area of the road increase before US 206 widens to four total lanes and comes to a modified cloverleaf interchange with I-80 and the southern terminus of Route 183.

[9] The freeway continues northwest, running through a small corner of Netcong before coming back into Mount Olive and interchanging with US 46.

[3][9] Immediately after US 46, the highway passes over NJ Transit's Morristown Line/Montclair-Boonton Line before turning north and reaching a trumpet interchange where US 206 splits from I-80.

[9] Following this split, US 206 is a four-lane freeway that heads northeast, crossing under Waterloo Valley Road and an abandoned railroad line before coming to an interchange with International Drive.

Immediately following the river crossing, the freeway merges with the northern terminus of Route 183 at an interchange on the border between Byram Township to the west and Stanhope to the east.

[3] The route continues into Andover, where it becomes Main Street and passes under the abandoned Lackawanna Cut-Off and intersects with Brighton Avenue (CR 517).

Here, the route bypasses the center of town to the south as a four-lane divided highway before crossing the intersection of Newton Avenue (CR 519).

[10] A short distance after the bridge, the route comes to a northbound toll plaza, where it becomes a two-lane divided highway.

The Crosswicks and Trenton Turnpike was chartered in 1854; the road is now locally known as Broad Street, and was included in US 206 west of White Horse.

The road is to meet a Smart Growth goal by preserving land and eliminating two planned interchanges that would have increased congestion.

The final phase of the US 206 Bypass, which is projected to cost $36.6 million and be funded through state and federal money, opened on June 5, 2021.

First crossing over CSX's Trenton Subdivision railroad line, it curves to the north and comes to a signalized intersection of Hillsborough Road.

Continuing north, the bypass passes through farmland and woodland with some nearby development, coming to bridges over Homestead Road and the Trenton Subdivision.