Commuters from the Selby area, travelling to work in the York area, are to have one of their "escape" routes blocked for up to a fortnight.
The B1222, which runs via Cawood, Stillingfleet and Naburn, joining the A19 at Fulford, is to be closed from Monday so that a new flood-water pipe can be laid.
It could mean extra delays for motorists travelling to work in and around York who use the road to avoid rush-hour traffic and Selby swing bridge.
The work is being carried out in Naburn Lane, near Fulford, but the 7ft trench needed for the pipe effectively seals off the "back road" route from Selby and surrounding villages to York.
Meanwhile, angry residents in an isolated row of houses on the lane are up in arms after being told they are to be isolated from the rest of their village by the roadworks.
About 13 homes have been told they will be cut off from the rest of their village when work starts.
It means the usual trip of less than half a mile into Fulford has been extended to about five miles.
"Normally, we can just walk straight into the village, but this work means we won't be able to get through," said resident Andrew Turner.
"Now we're going to have to go into Naburn village and over to Fulford by Crockey Hill, which is about five miles."
The work, which is being carried out by Caddick Construction, is to lay a drainage pipe from a new retail development at the old Naburn Hospital to the river.
It means the road could be closed for up to two weeks while a seven-foot trench cuts the road in two.
The houses are on the wrong side of the split, unable to get to the village only a few hundred metres away.
Buses used by many of the residents have been stopped, and appeals for a replacement taxi service have been rejected.
Mr Turner said: "A lot of the people who live here are elderly or don't own their own cars. I don't see how they are going to be able to get into Fulford if their isn't any other service."
A spokesman for York City Council, which was consulted about the closure plans, said: "We see the plans and we can modify them, but if the work needs to be done it is not in our power to stop it.
"In this instance we have looked at it and there is no way round it other than road closure."
She added that Caddick Construction had told them that alternative pedestrian and cycling access to the village was being provided.But a resident who lives nearby and who asked not to be named, said: "There are signs in place pointing out pedestrian access, but we can't see how we'll be able to use it when there's a seven-foot hole in the way.
"A lot of people here are very angry at what's happening and the way the people who live here are being treated. We've had to put up with a lot because of the work on the retail park, but we don't seem to have been given any consideration."
That was denied by Caddick Construction contract manager Colin Stainthorpe.
He said: "The local people have had a lot of consideration.
"Discussions with the city council have been going on for a number of weeks, trying to find a feasible alternative, but unfortunately there just isn't one.
"For the safety of the public and our operatives we have to close the road, but we are keeping the time that it's closed down to an absolute minimum."
He added that access for pedestrians and cycles would be provided.
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