Interstate 376 (I-376) is a major auxiliary route of the Interstate Highway System in the US state of Pennsylvania, located within the Allegheny Plateau. It runs from I-80 near Sharon south and east to a junction with the Pennsylvania Turnpike (I-76, its parent) in Monroeville, after having crossed the Pennsylvania Turnpike at an interchange in Big Beaver. The route serves Pittsburgh and its surrounding areas and is the main access road to Pittsburgh International Airport (PIT). Portions of the route are known as the Beaver Valley Expressway, Southern Expressway, and Airport Parkway. Within Allegheny County, the route runs along the majority of the Penn-Lincoln Parkway, known locally as Parkway West and Parkway East. It is currently the ninth-longest auxiliary Interstate route in the system and second only to I-476 within Pennsylvania.

I-376 is signed east–west despite running north–south for nearly three-quarters of its length; however, it does run east–west through the majority of Allegheny County. This is because, until 2009, the route's western terminus was at I-279 in Downtown Pittsburgh; it was extended west and north to I-80 to give the corridor a single route designation. Despite the route's direction, it serves as a major artery through Pittsburgh's West End, with I-79 being the primary route through Pittsburgh's North Hills. Since its 2009 extension, the route has also served as a major way to access Northeast Ohio.

A 16-mile (26 km) stretch of the Beaver Valley Expressway, officially named the James E. Ross Highway, from exit 15 where I-376 ends its brief concurrency with U.S. Route 422 (US 422) to exit 31 where I-376 has its first interchange with Pennsylvania Route 51 (PA 51), is tolled and is maintained by the Pennsylvania Turnpike Commission (PTC), while the remainder of the highway is maintained by the Pennsylvania Department of Transportation (PennDOT). Near the airport, I-376 also has a business loop.

I-376 begins at a cloverleaf interchange with I-80 and PA 760 located four miles (6.4 km) east of Ohio within the Glaciated Allegheny Plateau. From there, it travels in a southerly direction on the Beaver Valley Expressway, a four-lane freeway with a wide grass median. Paralleling PA 18, I-376 has its first interchange with that state highway in West Middlesex.

I-376 soon meets US 422 and forms an overlap with that highway along the west side of New Castle. After an interchange with US 224 in Union Township, I-376 eastbound splits from US 422 at a trumpet interchange southwest of the city in Taylor Township. At this point, I-376 becomes a toll road officially named the James E. Ross Highway.

I-376 continues southward, still paralleled by PA 18 and the Beaver River to the east. Shortly after entering Beaver County near Koppel, the route connects to its parent route I-76 (Pennsylvania Turnpike) for the first time at an interchange which also provides access to PA 351. Around this area, I-376 crosses into the Unglaciated Allegheny Plateau, where it remains for the remainder of its length.

I-376 then passes to the east of West Mayfield and becomes a non-tolled highway again at its first interchange with PA 51 in Chippewa Township, just west of Beaver Falls. The freeway then weaves through mountainous terrain, interchanging with PA 68 in Vanport just before crossing the Vanport Bridge over the Ohio River. It then has its second interchange with PA 18 near Kobuta and continues south from there. I-376 passes to the west of Aliquippa before leaving Beaver County and entering Allegheny County.

Approaching PIT, I-376 bends south-southwest and becomes the Southern Expressway, while the Beaver Valley Expressway diverges to the southeast along I-376 Business (I-376 Bus). I-376 circles around the southern edge of the airport, intersecting the western terminus of the Southern Beltway (PA Turnpike 576) at the main entrance to PIT before recombining with I-376 Bus and becoming the Airport Parkway, still four lanes and with a narrow median.