Mulgrew has performed in multiple television shows, theatre productions and movies, she has also earned multiple awards for her acting, including an Obie Award, a Golden Satellite Award and a Saturn Award. She has also been nominated for a Golden Globe Award.

She is also an active member of the Alzheimer's Association National Advisory Council and the voice of Cleveland's Metro Health System.

Mulgrew was born April 29, 1955 in Dubuque, Iowa, to Thomas James "T.J." Mulgrew II, a contractor, and Joan Virginia Mulgrew (née Kiernan), an artist and painter.

Born into an Irish Catholic family, she is the second oldest of eight siblings.

At the age of 17, Mulgrew was accepted into the Stella Adler Conservatory of Acting in conjunction with New York University in New York City. Mulgrew left NYU after her junior year, receiving her Associate of Arts degree in 1976.

Her early career included portraying Mary Ryan for two years on the ABC soap Ryan's Hope (1975) She became a fan favorite and is still associated with the show long after its cancellation. Mulgrew remains friends with former co-star Ilene Kristen and presented a special Soap Opera Digest Award to Ryan's Hope creator Claire Labine in 1995.

While in Ryan's Hope she also played the role of "Emily" in the American Shakespeare Theatre production of Our Town in Stratford, Connecticut. In 1979, she began playing Kate Columbo in Mrs. Columbo, a series created specifically for her.

In 1993, Mulgrew separated from her husband, Robert H. Egan, with whom she had been married for 12 years. In 1995, the divorce became final, and she was on the verge of having to sell her house and move into an apartment in Westwood[disambiguation needed] when she was called to take the part of Captain Kathryn Janeway in Star Trek: Voyager. Geneviève Bujold, who had been cast in the role, left two days into filming, stating that a television series work schedule was too demanding. Mulgrew made history in the Star Trek franchise when she became the first female captain as a series regular in a leading role. Voyager was the first show broadcast on the new UPN channel and also the only television show on UPN to run for seven seasons, making it the network's longest running show, and the only show left over from its first year. Mulgrew won the Saturn Award for "Best TV Actress" in 1998 for her performances as Janeway. Mulgrew also voiced the character of Janeway in the PS2 and PC game Star Trek: Voyager - Elite Force and Star Trek: Voyager - Elite Force 2. PC Gamer UK rated the game Star Trek: Voyager - Elite Force 93% and fans consider this game to be one of the best Trek games of all time.

During Voyager she also played the role of Titania in the animated series, Gargoyles and Victoria Riddler in Riddler's Moon, a made for TV movie.

Mulgrew is also one of six Star Trek actors to lend their voice to Star Trek: Captain's Chair, reprising her role as Captain Kathryn Janeway. The others five actors were Jonathan Frakes, Michael Dorn, George Takei, Avery Brooks and Majel Barrett.