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Route 406 begins at an intersection with Route 1 (Trans-Canada Highway) in and heads west along the banks of the to pass through Upper Ferry, where it has an intersection with a local road leading to Searston and Loch Lomond, as well as cross a bridge over the river. The highway makes a sharp left at an intersection with a local road leading to O'Regan's to follow the northern banks of the river westward through Great Codroy and Millville, where it has an intersection with Route 407 (St. Andrew's-Searston Road). Route 406 begins fill the coastline of the Gulf of St. Lawrence as it heads northwest through Woodville, Codroy, and the community of Cape Anguille, with provincial maintenance coming to shortly after meeting a road to the point of Cape Anguille and the Cape Anguille Lighthouse.
Route 1 (TCH) in 
Route 407 in Millville
