Stagecoach has announced that the 113 service from Wigan to Preston will be axed from January 2019.
The service travels through Standish, Wrightington, Heskin, Eccleston, Croston, Ulnes Walton, Leyland, Lostock Hall, Bamber Bridge, and Walton-le-Dale before arriving in Preston.
Lancashire County Coun for Chorley Rural East, Kim Snape, said: “I have been inundated by residents with their concerns over the recent news from Stagecoach to withdraw this service.
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"This will leave large parts of South Ribble, Leyland and the surrounding villages of Ulnes Walton, Croston and Eccleston with little or no alternative.
"Public transport is key to school, work, life and to not isolate people in their communities.
"Sadly Stagecoach have announced that the reason for this announcement is the service has become unviable to operate. I would call upon them to think again and have discussions with partners and interested parties to seek a better way forward.”
Paul Sloan, Croston resident and campaigner, said “Lots of residents in the Ulnes Walton, Croston and Eccleston area are concerned about how they will get to work, shops and most importantly maintain their independence.
"I am appalled that Stagecoach have left us in this situation. Sadly Stagecoach only seem to be interested in profit and not providing a public service."
Chair of Heskin Parish Council, Coun Angela Bamber, said: “This will be a severe blow to ours and neighbouring villages, especially the young and elderly who rely heavily on a bus service.
"On a personal note, I am wondering how my granddaughter and fellow students continue their education at Wigan and Leigh College without the means of getting there."
Chorley Coun Alan Whittaker added: "The bus is a lifeline for so many people."
"Plainly Stagecoach are trying to get subsidy from Lancashire County Council . They opted to run this service as a commercial route and knew full well the income they could expect. I shall be asking Stagecoach to reconsider their decision and also ask Lancashire County Council the importance of this route in relation to subsidies."
A Wrightington Parish Council spokesman said: "This service is a lifeline to the residents of Wrightington, who use this service, to access doctors, opticians, the post office, supermarkets and much more, none of which exist in Wrightington.
"The loss of this bus service will result in social isolation for many elderly and disabled residents in our rural parish and the Parish Council will be fighting to retain this service."
In a statement, Stagecoach said: "From Monday January 7, service 113 between Preston and Wigan will be withdrawn.
"This is not a decision the business has taken lightly.
"We have exhausted all options to keep the service in operation, but there has been a significant decline in the number of passengers over a long period of time and without financial assistance, the route is unfortunately no longer viable.
“Stagecoach made Lancashire County Council aware of its decision well in advance and we will be working closely with them to assist them where possible in providing alternative transport arrangements for communities affected.”
In an email to Lancashire County Councillors, Ashley Weir - the county council's Principal Transportation Officer for Local Bus, said: "This is likely to cause some concern among those customers who use the service and has been brought to the attention of the County Councillor Keith Iddon, Cabinet Member for Highways and Transport.
"We will be exploring with alternative service providers if any possible sustainable solutions can be achieved."