Route 45 is a state highway in the southern part of New Jersey, United States. It runs 28.51 mi (45.88 km) from Route 49 in Salem, Salem County, northeast to U.S. Route 130 in Westville, Gloucester County. Much of the southern part of the route runs through rural areas of Salem and Gloucester counties, passing through the communities of Woodstown and Mullica Hill. North of Mullica Hill, Route 45 runs through suburban areas, with the portion of the route between the northern border of Mantua Township and the southern border of Woodbury a four-lane divided highway. The route intersects many highways, including U.S. Route 40 in Woodstown, Route 77 and U.S. Route 322 in Mullica Hill, and Interstate 295 in West Deptford Township.

The current route was originally a segment of pre-1927 Route 6 that was created in 1917, running from Salem to Camden. Route 45 was designated in 1927 to replace the Salem-Camden branch of pre-1927 Route 6 and was eventually realigned to follow U.S. Route 130 (Crescent Boulevard) to the Airport Circle in Pennsauken Township. The northern terminus of Route 45 was moved to its current location in 1953 in order to avoid the concurrency with U.S. Route 130. A freeway for Route 45 between Interstate 295 in Woodbury and U.S. Route 322 in Mullica Hill was recommended by the Delaware Valley Regional Planning Commission in the 1960s. It was never built, and the New Jersey Department of Transportation proposed widening all of Route 45 into a four-lane divided highway; only a small portion in northern Gloucester County was widened.

Route 45 begins at an intersection with Route 49 in Salem, Salem County, heading to the north on Market Street, a two-lane undivided road. It passes downtown businesses and both the Salem County Courthouse and the Old Salem County Courthouse, the second oldest active courthouse in the United States, which currently serves as the Salem City Court. Upon crossing County Route 657, the road heads into residential areas before crossing a Southern Railroad of New Jersey railroad line and the Fenwick Creek. At the crossing of the latter, Route 45 enters Mannington Township and becomes an unnamed road passes marshland with some commercial establishments and homes. The route passes by the Memorial Hospital of Salem County just prior to an intersection with County Route 540 in Pointers. Here, Route 45 turns to the east and forms a concurrency with County Route 540, passing some homes before heading into farm fields with occasional residences. County Route 540 splits from Route 45 by heading southeast on Welchville Road and Route 45 continues through more agricultural areas, intersecting County Route 653 before crossing the Mannington Creek and heading northeast through a mix of woods and farms. It intersects County Route 669 and County Route 631 within a short distance of each other before crossing Majors Run into Pilesgrove Township.

Here, the route intersects County Route 679 near the Salem County Veterans Cemetery before heading through more agricultural areas. The route reaches an intersection with U.S. Route 40 (Harding Highway) and County Route 616 in a business area, where U.S. Route 40 forms a concurrency with Route 45. The two routes head northeast into Woodstown as the Harding Highway, heading into neighborhoods. At the intersection with Main Street in the commercial downtown, Route 45 splits from U.S. Route 40 by heading north on Main Street while County Route 672 heads south on Main Street and U.S. Route 40 continues to the east on East Avenue. Route 45 continues north, intersecting County Route 636 before turning northeast again and meeting County Route 602. The road passes over a Southern Railroad of New Jersey line before coming to an intersection with County Route 668/County Route 617. A short distance later, the route enters Pilesgrove Township again and heads back into farmland with some residences and forested areas as an unnamed road, crossing County Route 660.

Route 45 crosses Oldmans Creek into South Harrison Township, Gloucester County within woodland, where it continues northeast through more rural farms and forests with some residential developments as Woodstown-Mullica Hill Road. The route crosses County Route 668 before crossing County Route 694 and County Route 607 within a close distance of each other. Past this intersection, it continues to County Route 617, where the name changes to Woodstown Road, before crossing County Route 538. A short distance later, the route enters Harrison Township and continues north. It enters the wooded residential community of Mullica Hill, where it intersects the northern terminus of Route 77. Here, Route 45 turns north and becomes Main Street, passing more homes and some businesses.

In Mullica Hill, the road crosses U.S. Route 322 and County Route 536, and Route 45 continues northeast along Main Street, passing residential neighborhoods with some commercial establishments. The route intersects County Route 664, County Route 603, County Route 667, and County Route 624 before crossing into Mantua Township, where it becomes Bridgeton Pike. The road heads through a mix of woods and farms with occasional homes, intersecting County Route 626. The route passes more fields and a patch of woods past this intersection before heading into suburban development. Here, Route 45 intersects County Route 627 and County Route 678 before continuing into business areas. The route intersects County Route 632, where the name changes to Mantua Pike, and County Route 553 Alternate before widening into a four-lane divided highway and crossing the Mantua Creek. At this point, Route 45 turns to the north and forms the border between Deptford Township to the east and West Deptford Township to the west. The road heads through residential and business areas, intersecting County Route 648 and County Route 656. At the intersection with College Boulevard, the route forms the border between Woodbury Heights to the east and West Deptford Township to the west, crossing over the New Jersey Turnpike without an interchange. From here, Route 45 continues past commercial establishments, intersecting County Route 652 and County Route 650.

After the intersection with the latter, the route becomes a four-lane undivided road, entering Woodbury and immediately crossing a Conrail Shared Assets Operations railroad line. The road crosses another railroad line before coming to an intersection with County Route 551. Here, Route 45 forms a concurrency with County Route 551 and heads north-northeast on Broad Street through the downtown of Woodbury. The road intersects County Route 663 and continues through the downtown. Route 45 and County Route 551 cross the Woodbury Creek out of the downtown area and intersect County Route 644 near Underwood-Memorial Hospital. From here, the route continues past a mix of residences and businesses as a two-lane undivided road. County Route 551 splits from Route 45 by heading east on Park Avenue then north on Broadway. Meanwhile, Route 45 continues north along the border between Deptford Township to the east and Woodbury to the west, with a Conrail Shared Assets Operations railroad line closely paralleling the route on its east side. At the intersection with County Route 642, the road forms the border between Deptford Township and West Deptford Township again and passes homes. The route widens into a four-lane divided highway as it comes to a partial interchange with Interstate 295, with some of the movements provided by nearby County Route 551 to the east. Past this interchange, Route 45 becomes a four-lane undivided highway and enters Westville. Here, it continues parallel to the railroad line to the east with businesses lining the west side of the road. Route 45 passes residential areas before it comes to its northern terminus at a directional Y-intersection with U.S. Route 130.

What is now Route 45 was originally designated as a segment of pre-1927 Route 6 in 1917. This route was to head south from Camden and follow Route 45 to Mullica Hill, where it split into two branches, with one going to Salem on current Route 45 and another going to Bridgeton on current Route 77. In the 1927 New Jersey state highway renumbering, pre-1927 Route 6 between Camden and Salem became Route 45. A bypass around Camden was created as the southern half of Crescent Boulevard, a part of U.S. Route 130, and Route 45 was rerouted to use the bypass up to the Airport Circle in Pennsauken Township. In the 1953 New Jersey state highway renumbering, the northern terminus of Route 45 was cut back to its current location in Westville to avoid the concurrency with U.S. Route 130.

In the late 1960s, the Delaware Valley Regional Planning Commission (DVRPC) proposed construction of a 10-mile (16 km) long, $20 million freeway along the Route 45 corridor in Gloucester County which would have extended from Exit 24 of Interstate 295 in Woodbury to a planned U.S. Route 322 freeway in Mullica Hill. The New Jersey Department of Transportation never followed through on this proposal, instead proposing a widening project to create a four-lane divided highway for the full length of Route 45 from Woodbury to Salem, of which only a small portion was ever completed by the 1980s, running from the border of Woodbury to the border of Mantua Township. In 2012, the Mullica Hill Bypass was completed, and US 322 was removed from its concurrency with Route 45.