The Chesapeake and Ohio Canal Scenic Byway heads east on MD 478 into Brunswick, which is the location of the Brunswick Heritage Museum and a Visitor Center. The byway continues along MD 464 to Point of Rocks, which is where the Baltimore and Ohio Railroad met the Chesapeake and Ohio Canal. From here, the byway follows MD 28 across the Monocacy Natural Resource Management Area, with a spur leading to Sugarloaf Mountain. The Chesapeake and Ohio Canal Scenic Byway heads south on MD 109 into Poolesville, where the John Poole House and the Seneca Schoolhouse is located. A side route on the byway heads west to the White's Ferry across the Potomac River. Another branch off the byway runs through areas protected by the Montgomery County, Maryland Agricultural Reserve, with the road continuing along MD 118 to Germantown, a small town with antique shops. The mainline of the byway continues through Seneca Creek State Park and picks up MD 190 (River Road), continuing along the canal towpath. The byway turns south onto Falls Road and comes to the Great Falls of the Potomac River. From here, the Chesapeake and Ohio Canal Scenic Byway heads east along MacArthur Boulevard before continuing onto the Clara Barton Parkway. The road has access to the Clara Barton National Historic Site before reaching Washington, D.C. and continuing to Georgetown.