While the road was under construction, it was predicted that economic conditions would improve along the corridor for the five counties connected by I-68: Allegany, Garrett, and Washington in Maryland and Preston and Monongalia in West Virginia.

[3] In the early 1960s, as the Interstate Highway System was being built throughout the U.S., east–west travel through western Maryland was difficult, as US 40, the predecessor to I-68, was a two-lane country road with steep grades and hairpin turns.

[6] This portion of the highway, which consists of a mile-long (1.6 km) elevated bridge, was completed and opened to the public on December 5, 1966.

The first corridor for the construction to be approved by the Maryland State Highway Administration (MDSHA) ran south of US 40.

This proposed corridor provoked strong opposition, largely due to the environmental damage that would be caused by the road construction in Green Ridge State Forest.

Environmental groups sued MDSHA in order to halt the planned construction, but the court ruled in favor of the state highway administration.

In 1984, however, MDSHA reversed its earlier decision and chose an alignment that closely paralleled US 40, passing through Flintstone and to the north of Green Ridge State Forest.

In the 1980s, the project to improve US 50 between Washington DC and Annapolis to Interstate Highway standards had been assigned the designation of I-68.

[17] This made the designation to be applied to that freeway more flexible, and so, in 1989, the American Association of State Highway and Transportation Officials (AASHTO), the organization composed of the various state departments of transportation that decides route numbering in the U.S., approved MDSHA's request to renumber the US 50 freeway from I-68 to I-595.

[21][22][23] On May 23, 2003, poor visibility due to fog was a major contributing factor to an 85-vehicle pileup on I-68 on Savage Mountain west of Frostburg.

[26] One of the arguments in favor of the construction of I-68 was that the freeway would improve the poor economic conditions in western Maryland.

[32] In 2014, Marshall County officials brought the extension of I-68 up again as a way for oil companies to have easier access to drill into the area, likely by fracking.

Much like the second leg of PA 576 (Southern Beltway) in the Pittsburgh area, an extension of I-68 is being spurred in response to the Marcellus natural gas trend.

If the extension were to be built, it would also include a widening of WV 2 to four lanes and would cost an estimated $5 million per mile ($3.1 million/km).

[34] I-68 spans 113.15 miles (182.10 km), connecting I-79 in Morgantown, West Virginia, to I-70 in Hancock, Maryland, across the Appalachian Mountains.

The control cities—the cities officially chosen to be the destinations shown on guide signs—for I-68 are Morgantown, Cumberland, and Hancock.

[37] I-68 begins at exit 148 on I-79 near Morgantown and runs eastward, meeting with US 119 one mile (1.6 km) east of its terminus at I-79.

Leaving the Morgantown area, I-68 again runs eastward, intersecting WV 43, which provides access to Cheat Lake and Uniontown, Pennsylvania.

[38] Entering Preston County, the route intersect CR 73/12, which provides access to Coopers Rock State Forest.

In contrast to the Morgantown area, the portion of Preston County that I-68 crosses is more rural, with the only town along the route being Bruceton Mills.

I-68 meets CR 5 (Hazelton Road) at its last exit before entering Garrett County, Maryland.

There are several sections that have steep grades, especially near the Cheat River Canyon, where there is a truck escape ramp.

The traffic gradually decreases further eastward, reaching a low point at 14,600 vehicles per day at the Hazelton exit.

I-68 crosses Negro Mountain, which was the highest point along the historic National Road that the freeway parallels east of Keysers Ridge.

[4] Three miles (4.8 km) east of Grantsville, US 219 leaves the National Freeway to run northward toward Meyersdale, Pennsylvania, while I-68 continues eastward, crossing the Eastern Continental Divide and Savage Mountain before entering Allegany County.

In Allegany County, the freeway crosses the Allegheny Front, where, from Savage Mountain to LaVale, the highway drops in elevation by 1,800 feet (550 m) in a distance of nine miles (14 km).

In Allegany County, the vehicle count increases to 28,861 in LaVale and to the freeway's peak of 46,191 at the first US 220 interchange (exit 42) in Cumberland.

East of Cumberland, the vehicle count decreases to 16,551 at Martins Mountain and stays nearly constant to the eastern terminus of I-68 in Hancock.

[43] East of Frostburg, I-68 crosses a bridge above Spruce Hollow near Clarysville, passing over MD 55, which runs along the bottom of the valley.

I-68 continues across northeastern Allegany County, passing Rocky Gap State Park near exit 50.