Over 1,000 people have signed an online petition calling for a new A6 bypass between High Lane, Disley and Furness Vale "as an urgent priority".
The petition at Change.org is addressed directly to Prime Minister Boris Johnson and demands a bypass be built to alleviate congestion and pollution in areas such as High Lane, Disley, Newtown and Furness Vale.
It has been organised by Disley resident Simon Brownbill, who regularly uses the route to travel to and from work in Stockport.
The petition has so far attracted around 1,500 signatures, including 500 within the first 24 hours after it went live.
Mr Brownbill said: "A bypass is the number one priority for most residents living along the route.
"We desperately needed one anyway, but since the new A555 opened the congestion, pollution, and rat-running has increased dramatically.
"It's also really unsafe for cyclists and there isn’t enough room for bus lanes or cycle routes that might alleviate traffic volume."
Mr Brownbill, who is also a Disley parish councillor, said there was an argument for support from central government.
“This part of the A6 passes through relatively small parts of Greater Manchester, Cheshire East and Derbyshire," he added.
"As a whole, the route affects thousands of people every day, but no-one seems to look at things holistically."
A bypass for the area was last formally tabled in 1989 and included consultations with residents on three planned routes, but it was shelved due to budget restrictions.
The Advertiser reported last month how residents in Furness Vale were campaigning to improve road safety through their village, with over 400 people signing a separate petition calling for speed cameras to be installed.
Campaigner William Garratt, 72, who lives on Buxton Road in Furness Vale, said action needed to be taken before there was a ‘nasty accident’.
He said: “This road is getting more and more dangerous, especially now the (Manchester) airport relief road has opened but nobody is listening to us.
“We feel forgotten as we only ever see a councillor here when it’s election time and we have been left with a road that is going have a nasty accident on it because drivers won’t slow down."
William said a mobile speed camera unit did visit the village and helped to slow down the traffic.
But he added that if the county council was not prepared to install fixed speed cameras, it should consider other measures such as more warning signs.