I-70 meets US 40 (National Pike) at a cloverleaf interchange as the two highways leave the suburban area surrounding Hagerstown. The Interstate curves to the southeast and has a diamond interchange with MD 66 (Mapleville Road) near Beaver Creek. I-70 crosses Beaver Creek and Black Rock Creek and gains an eastbound climbing lane as the highway ascends South Mountain and passes through Greenbrier State Park. At the top of the mountain, the Interstate passes under US 40 and the Appalachian Trail and enters Frederick County. I-70 has a pair of rest areas on the east side of the mountain, one per direction.
I-70’s eastbound climbing lane disappears and the Interstate has a westbound climbing lane from the top of the mountain southeast to a diamond interchange with MD 17 (Myersville Middletown Road) south of Myersville, where the freeway enters the Middletown Valley. Within the valley, the Interstate crosses Catoctin Creek and Little Catoctin Creek. I-70 gains an eastbound climbing lane as it climbs Braddock Mountain, on top of which the freeway passes under a concrete arch bridge carrying Ridge Road. Westbound I-70 has a climbing lane as the highway descends Braddock Mountain and has partial interchanges with US 40 (National Pike) and US 40 Alternate (Old National Pike). The first interchange is a pair of flyover ramps from eastbound I-70 to eastbound US 40 and from westbound US 40 to westbound I-70. The second interchange is a half diamond interchange with an exit ramp from westbound I-70 to US 40 Alternate, and an entrance ramp to eastbound I-70.
After entering the Frederick Valley, I-70’s speed limit drops from 70 to 65 mph (115 to 105 km/h). The Interstate passes under MD 180 (Jefferson Pike) and has a partial interchange with Jefferson National Pike, a freeway that carries US 15 and US 340; eastbound I-70 has ramps to both eastbound and westbound US 15 / US 340, while westbound I-70 has only a flyover ramp to westbound Jefferson National Pike. Eastbound I-70 receives a ramp from MD 180 and Ballenger Creek Pike and crosses over the state highway before reaching a directional interchange with I-270 and US 40. I-270 heads south toward Washington as Eisenhower Memorial Highway, taking over the name from I-70, while US 40 (Frederick Freeway) exits to the north and joins I-70 in a concurrency. I-70 heads east as a six-lane freeway and meets MD 85 (Buckeystown Pike) at a single-point urban interchange south of downtown Frederick. MD 85 is used to access MD 355 (Urbana Pike). The Interstate reduces to four lanes before it crosses over the Frederick Branch of CSX’s Old Main Line Subdivision. On the east side of Frederick, I-70 has a four-ramp partial cloverleaf interchange with South Street and a partial diamond interchange with MD 144 (Patrick Street).