An open congressional seat in the Merrimack Valley offers a prime opportunity for aspiring pols — enough so that several have moved into retiring US Representative Niki Tsongas’s district to run for the seat.

If history is any guide, this will not work out well — but that hasn’t stopped a slew of Democrats with varying levels of roots in the district from such attempts.

Mayor Martin J. Walsh’s chief of staff, Dan Koh, quit his job to return to his family’s Andover home to run for the office. He’s joined by a Cambridge city councilor, Nadeem A. Mazen, also an Andover native, who is claiming residence in the town, too.

A North Andover restaurant and hotel owner, Abhijit “Beej’’ Das, moved into the district in October and declared his candidacy. Barack Obama’s US ambassador to Denmark, Rufus Gifford, who grew up 30 miles away from the district’s border in Manchester-by-the-Sea, is showing strong interest in jumping into the race.

They follow a series of candidates — John Kerry being the most prominent and controversial — who have looked to the district as a steppingstone to Congress.

“There is a long history here when the district rejected people who would move in and run for Congress,’’ said Kendall Wallace, a veteran Lowell newsman who grew up in city’s Highland section. “There was a real resentment over candidates who felt they could come in and buy the district.’’

They are often called “blow-ins,’’ candidates looking to launch their careers by taking up residence in places like Lowell, the city at the heart of the congressional district with a tradition of gritty politics.

Kerry’s appearance in a 1972 Democratic primary was the most explosive. Claiming his roots were in his parents’ home in Groton, he “blew in’’ to Lowell 45 years ago at age 29, touting his career as a decorated naval lieutenant turned national antiwar hero.

It was ugly. He edged out a crowded primary, prompting many of the local Democrats to turn on him. The party, the local media, and, eventually, the electorate, took deep offense at what many saw as a Yale-educated elitist using the district as a political steppingstone.

Shaken and chastened by his general-election defeat, Kerry left the city after his brief residency. He relocated to Newton, and later Beacon Hill, and eventually became a US senator, a presidential nominee, and US secretary of state.

But there are a slew of others, mostly long forgotten, who tried to claim the seat. One was US Senator Edward Markey’s younger brother, John, although he didn’t stir as much ire as Kerry when he tried to lay claim to his family’s Lawrence connections and moved to the city. Markey still got blown away in a 1978 congressional primary. He went on to a successful law career in Boston.

Even Tsongas herself — the widow of local political icon Paul Tsongas, a born-and-bred Lowellian, US senator, and presidential candidate — faced the carpetbagger label when she ran for the seat in a 2007 special election. Niki Tsongas was born and raised outside the area, and she came to the city after she married her husband, then a newly elected city councilor, in 1970.

Despite her decades-long connections to the city, she failed to carry Lowell and much of its suburbs in part because of the issue. But by running strong in other parts of the district, Tsongas was able to edge out Lowell’s state senator, Eileen Donoghue.

“That was a signal to me the voters up there like people they know,’’ said David Paleologos, director of the Political Research Center at Suffolk University. “They tend to be parochial. Here’s the wife of a local hero, with high name recognition, having all those dynamics going for her, and then the district reverts back to granular politics.’’

That’s the local history candidates like Koh face. And it will be a hurdle for Mazen, a 33-year-old two-term city councilor in Cambridge and the state’s highest-profile Muslim elected official. He also grew up in Andover but hasn’t lived there since a few months after graduate school in 2009.

Another candidate, Das, who owns a high-end Tyngsborough restaurant, The Stonehedge Hotel and Spa, has moved from his hometown of North Andover, which is not in the district, to a condominium in Lowell’s downtown to launch his political career.

Koh, who quieted some heavy skepticism about his candidacy when he raised an incredible $750,000 in his first weeks of running, says he is ready to face the “blow-in’’ questions. He cites his family’s roots in Lawrence and his determination to get to as many voters as possible to make his case.

“At the end of the day it will be about the candidate who is out there meeting the voters and talking about the issues that concern them,’’ said Koh, who most recently resided in Boston’s West End.

“I have been door-knocking in Lowell, attending events all over the district,’’ he said. “It will be hard work, but anyone who knows my family story in this district knows my great-grandfather worked in the mills in Lawrence and my grandfather opened a medical practice in Lawrence that is now run by my mother.’’

Wallace, the longtime Lowell newsman, says that sort of argument will resonate much better than in past decades because of the change in demographics. He says the area is much more welcoming and has embraced the changes that include an influx of Cambodians, Hispanics, and African refugees.

“While there is still a hard-core [group] who will vote parochial . . . there is a whole new generation, many of whom have moved to the towns, who are open-minded,’’ said Wallace.

Still, the outsider reputation is something with which even local candidates contend. State Senator Barbara L’Italien, whose district takes in Andover, Lawrence, and Dracut, has lived for years in Andover — but in a precinct that only borders the Third District. A US representative is legally required to reside in the state, but not the district he or she represents.

Still L’Italien feels she lives close enough that she can sniff at candidates like Koh — even if she can’t vote for herself if she runs.

“While others are moving into the district from far away to give the appearance they are putting down roots here, I can proudly say I’ve lived here in the Merrimack Valley since 1967 and I’m not going anywhere after this election,’’ L’Italien said in a statement she released earlier this fall.

Frank Phillips can be reached at frank.phillips@globe.com.