Route 49 heads southwest on Broadway from an interchange with the New Jersey Turnpike, I-295, and US 40 in the community of Deepwater in Pennsville Township, Salem County, near the Delaware Memorial Bridge.

The route intersects CR 630 (Fort Mott Road) before it continues into farmland.

It turns left onto Broadway and forms the main business district of the town.

[1][2] Route 49 crosses a stream, Sarah Run, into Stow Creek Township, Cumberland County, and heads into farmland as Shiloh Pike.

The route then intersects CR 635 (Old Cohansey Road) and continues south along the border of Stow Creek Township to the west and Hopewell Township to the east, entering Shiloh at the intersection with Mill Road.

The route enters Hopewell Township and intersects CR 661 (Barretts Run Road).

[1] Past this intersection, Route 49 enters a more suburban landscape, crossing CR 621 (W. Park Drive).

It crosses CR 638 (N. Burlington Road) and enters Fairfield Township.

Route 49 heads east through the eastern part of Millville, crossing a Winchester and Western Railroad line and intersecting CR 678 (Wade Boulevard) before reaching an interchange with Route 55.

[1] Route 49 crosses the Tuckahoe River into Estell Manor, Atlantic County.

It runs a short distance to the north of the Tuckahoe River and intersects CR 649 (Aetna Avenue) and CR 666 (Cape May Avenue) at Head of the River Church.

From the west end of Bridgeton to the Salem-Cumberland line, then called Marlborough, was built by the Shiloh Turnpike Company, chartered in 1866.

[10] On October 1, 2008, the bridge over the railroad line in Tuckahoe was closed for reconstruction and reopened in June 2009.