[1] She ran in the Massachusetts' 5th Congressional District special election in 2007 to fill the United States House of Representatives seat vacated by Marty Meehan, narrowly losing the Democratic primary to Niki Tsongas.

In the Massachusetts Senate, Donoghue has been a staunch advocate for small businesses, economic development in gateway cities, and public higher education.

[7] In the general election Donoghue defeated Republican candidate James Buba and independent Patrick O’Connor, winning more than 54 percent of the vote.

She brought the committee on a statewide listening tour that included a stop in Lowell, where she highlighted how the local cultural community had fueled the city's renaissance.

[10] After negotiating agreements with the 17 unions that represent municipal employees, Lowell shifted its workers into the GIC and saved $7 million as a result.

[11] Donoghue also filed legislation creating a commission to study the feasibility, costs, and benefits of hosting the 2024 summer Olympics in Greater Boston.

[13] The commission concluded that hosting the Olympics was feasible, provided that new construction fit into the region's planning needs in the areas of infrastructure, housing, and economic development.

“The real value of a Boston Olympics was going to be the legacy it would leave behind,” she said at the time.” I’m excited to work for that legacy—with or without the Olympics.”[17] Donoghue became Senate chair of the Joint Committee on Economic Development and Emerging Technologies during her third term.

[18] In that role she helped usher through a billion-dollar economic development bill that invested in infrastructure, job creation, workforce training, and housing.

According to the Association of Independent Colleges and Universities of Massachusetts, Vermont introduced a similar tax incentive in 2006 and saw a 34 percent increase in the number of families opening savings accounts.

Donoghue also oversaw the Lord Overpass redesign,[28] a $25 million project that replaced aging, heavily utilized infrastructure and created a safer gateway to the City’s downtown.

Along with the City’s department of Planning and Development, Donoghue actively pursued and obtained grant funding to advance key economic development, open space improvement, and housing projects in Lowell, including a $1.7 million MassWorks grant [29] in 2021 to support a project aimed at creating affordable homeownership opportunities in the Acre neighborhood.

Donoghue led the City through two years of the COVID-19 crisis, working with state government and local partners to ensure the availability of testing, vaccination, and other resources for Lowell residents.