It begins at U.S. Route 2 (US 2) in Alburgh near the New York and Canada–US borders, and runs southeast to VT 105 in Sheldon.

It is one of two routes connecting the Vermont mainland to the Grand Isle area of Lake Champlain, the other being US 2 north of Burlington.

VT 78 begins at an intersection with U.S. Route 2 in Alburgh.

It crosses Lake Champlain onto the mainland, and proceeds southeast into the village of Swanton.

The two routes overlap very briefly, then VT 78 heads east through the village to an interchange with Interstate 89 at exit 21, just east of the village line in the town of Swanton.