I-81 is the primary north–south Interstate Highway in Washington County, connecting Hagerstown with Chambersburg and Harrisburg to the north and Martinsburg, Winchester, and Roanoke to the south.

Construction on the Hagerstown Bypass began in the mid-1950s and was completed in 1958 from US 40 north to the Pennsylvania state line.

Long-range plans call for widening I-81 to six lanes and effecting further interchange improvements along what is a major commuting and trucking corridor.

The Interstate curves to the northeast around Williamsport, where the highway meets Maryland Route 68 (MD 68) and MD 63 (Lappans Road) at a diamond interchange (exit 1) to the south of the town and US 11 (Virginia Avenue) at a five-ramp partial cloverleaf interchange (exit 2) to the east.

I-81 meets Halfway Boulevard, which leads to several shopping centers including Valley Mall, at a six-ramp partial cloverleaf interchange (exit 5).

The Interstate crosses CSX Transportation's Lurgan Subdivision railroad line and passes under MD 144 (Washington Street) with no access before reaching a cloverleaf interchange with US 40 (National Pike; exit 6).

The Interstate curves to the north and crosses Norfolk Southern Railway's Lurgan Branch.

The Interstate passes along the eastern edge of Maugansville, where the highway meets Maugans Avenue at a diamond interchange (exit 9).

[22][25][26] I-81 is heavily congested within Maryland due to the 1960s-era freeway being used as both a commuter route within the rapidly growing Hagerstown metropolitan area as well as a major trucking corridor.

In 2010, the highway had a minimum annual average daily traffic (AADT) of 43,771 between Showalter Road and PA 163 and a maximum of 62,181 between Halfway Boulevard and US 40.

[2] The Interstate is often used by long-distance traffic as an alternative to I-95 to avoid traveling through the major cities of the East Coast.

The state completed the planning process for the eventual upgrades to the Interstate Highway in November 2010.