The move comes after Alex Salmond delivered a keynote speech in Carlisle earlier this year, when he pledged to deliver a high-speed rail link between England and Scotland.
Better Together supporters are hoping to tap into the 3,000 Scottish voters it is estimated cross the Border every day for work.
No supporters have been handing out campaign materials and running street stalls in Carlisle, which is the nearest city for many living in Dumfries and Galloway and is on the West Coast mainline.
Dumfries and Galloway Labour MP Russell Brown – a shadow minister on Ed Miliband’s frontbench – said the campaigners were also targeting the 20 per cent of Carlisle residents who it is estimated have family in Scotland, in an attempt to lobby them to persuade their relatives to vote No next month.
The Labour MP said many people would find themselves having to travel to a foreign country to get to work in the event of a Yes vote.
He said: “There are 3,000 people who cross the Border to Cumbria to get to work every day in Carlisle and similar numbers in the other direction – there’s a real interdependency. During the campaign we’re meeting a considerable number of people in Carlisle, who are fairly regular visitors from Scotland and it’s a bit of an anxious time for them.
“Lots of people travel from Dumfries and Galloway to Cumbria to work.
“You would end up with people from Scotland working for companies based in Cumbria that become foreign companies overnight.”
Brown said the local campaign would step up its work in the run up to 18 September, with politicians such as Carlisle Conservative MP John Stevenson, originally from Aberdeen, in turn speaking at hustings over the Border in Gretna. Stevenson said the No campaign had to battle for every last vote ahead of polling day.
He said: “What’s striking about Carlisle is the large number of Scottish voices you hear when you go into the city centre on a Saturday to do some shopping. That’s why we’re campaigning here so much.
“From a personal perspective I’m a Scot – my mother is in Fife and I have a sister in Dunfermline. I do believe that Scotland and England are better off together. A Yes vote would be detrimental to both.”
He added: “There is a lot of cross-Border activity and I don’t see why you would want to put up borders to disrupt that when you don’t need to.”
Lee Sherriff, Labour’s Westminster candidate for Carlisle for the 2015 General Election, said a key message of the No campaign in the city was about what she said would be a “harmful Border affect”, with travellers potentially facing checks as they enter Scotland via Cumbria.
She said: “We’ve got very good cross-Border connections with a lot of people who work in Cumbria, but live in Scotland and vice versa.
“The physical barrier that we’d get with a Yes vote would cause a lot of problems for people coming and going in both directions.
“If people had to cross into a different country to get to work it would cause all sort of bureaucratic complications.”
Yes Scotland chairman Dennis Canavan said the pro-independence campaign was directing its energies north of the Border.
He said: “Yes Scotland is concentrating all its efforts on getting a positive message to communities across Scotland.”