Pennsylvania Route 72 (PA 72) is a 37-mile (60 km) long north–south state route located in southeast Pennsylvania. The southern terminus of the route is at U.S. Route 222 and Pennsylvania Route 272 in downtown Lancaster. The northern terminus is at Pennsylvania Route 443 north of Lickdale in Swatara Township. It crosses Interstate 81, U.S. Route 22, U.S. Route 422, U.S. Route 322, Interstate 76 and Pennsylvania Route 283.

PA 72 north begins at U.S. Route 222 and Pennsylvania Route 272, south of downtown Lancaster as Queen Street. PA 72 south begins at US 222 and PA 272, north of downtown Lancaster as Fruitville Pike. PA 72 north begins as Queen Street and intersects Pennsylvania Route 23 and Pennsylvania Route 462 in downtown Lancaster. PA 462 east as King Street, PA 23 east as Chestnut Street, and PA 23/462 west as Walnut Street. In the northern parts of Lancaster, PA 72 north has wrong-way concurrency with US 222 and PA 272 south. Then PA 72 north turns towards the north and splits from US 222/PA 272 at this point PA 72 is a two way road (Fruitville Pike) and has both northbound and southbound parts of PA 72.

In Manheim Township, PA 72 turns towards the northwest as Manheim Pike and leaves Fruitville Pike. Northwest of Fruitville Pike, PA 72 interchanges with U.S. Route 30. PA 72 only has access to US 30 west and only US 30 east has an exit to PA 72. Northwest of US 30, PA 72 interchanges Pennsylvania Route 283. Passengers on PA 72 can use PA 283 east to access US 30 eastbound. In East Petersburg, PA 72 becomes Main Street and intersects Pennsylvania Route 722. North of Petersburg, PA 72 becomes Lancaster Road and in Manheim, Main Street. In southern tip of Manheim, PA 72 begins a concurrency with Pennsylvania Route 772. In downtown Manheim is the northern terminus of the concurrency between PA 72 and PA 772. North of Manheim, PA 72 is called Lebanon Road. In Rapho Township, PA 72 parallels the Chickies Creek. Just south of the county border, PA 72 intersects Interstate 76 (the Pennsylvania Turnpike) at exit 266 (Lebanon - Lancaster exit). Currently there is some construction going on the PA turnpike interchange.

In West Cornwall Township, PA 72 begins a concurrency with U.S. Route 322 at a partial interchange. While merged with US 322, PA 72 interchanges Pennsylvania Route 117. Then US 322 separates from PA 72 at another partial interchange. PA 72 continues as Quentin Road and in Quentin, PA 72 intersects Pennsylvania Route 419. PA 72 continues north as Quentin Road. In the city of Lebanon, PA 72 meets the northern terminus of Pennsylvania Route 241. As PA 72 approaches downtown Lebanon, PA 72 south and north split. PA 72 intersects U.S. Route 422 also split into two streets. At the northern tip of Lebanon before the two PA 72 streets get back together, PA 72 meets the southern terminus of Pennsylvania Route 343. PA 72 continues out of Lebanon as Maple Street and Tunnel Hill Road. PA 72 is also called Ebenezer Road. In Union Township, PA 72 interchanges with U.S. Route 22 at a full Cloverleaf interchange. After PA 72 passes over Interstate 78, it meets Lickdale Road which takes passengers to Interstate 81 and Interstate 78. PA 72 continues north passing under I-81 into Swatara State Park and terminating (ending) at an intersection with Pennsylvania Route 443.