Fricker was born in Dublin, Ireland. Her mother, "Bina" (née Murphy), was a teacher at Stratford College, and her father, Desmond Frederick Fricker, was an officer in the Department of Agriculture and a journalist for The Irish Times. In her teens, she aspired to follow her parents' footsteps into journalism.
Before becoming an actress, Fricker was assistant to the art editor of the Irish Times, with hopes to become a reporter. At age 19, she became an actress "by chance", her feature film career began with a small uncredited part in the 1964 film Of Human Bondage, based on the 1915 novel by W. Somerset Maugham. She also appeared in Tolka Row, Ireland's first ever soap opera.
One of Fricker's first TV roles was staff nurse Maloney in Coronation Street, debuting on 10 January 1977. Brenda's character attended on the birth of Tracy Barlow on 24 January 1977's episode. Fricker came to wider public attention in the United Kingdom in another nursing role, as Megan Roach in the BBC One television drama series Casualty. Fricker bowed out as Megan in December 1990, after playing the character in 65 episodes, because she believed her character had "started off with a wonderful sense of humour, [but] lost it all and all she ever seemed to do was push a trolley around and offer tea and sympathy". In February 1998 she appeared in two episodes, with Megan attending the wedding of her former colleagues Charlie Fairhead and Barbara 'Baz' Samuels. In 2007, she returned for a single episode for Red Nose Day. The episode was written by Richard Curtis. Fricker's final appearance as Megan was in August 2010, when the character took a lethal cocktail of drugs to end her life.
Fricker found international acclaim after she won the 1989 Academy Award for Best Supporting Actress for her performance as Christy Brown's mother in My Left Foot. In her acceptance speech, Brenda thanked Christy Brown "just for being alive" and also dedicated the Oscar to Mrs. Brown, saying "Anybody who gives birth twenty-two times deserves one of these." For her performance Brenda was also nominated for a Golden Globe Award and she won the Los Angeles Film Critics Association Award for Best Supporting Actress as well. She rejoined My Left Foot's writer/director Jim Sheridan to make the 1990 film The Field, starring alongside Richard Harris as Maggie McCabe (wife of Harris' "Bull" McCabe). She continued her television work during this period, starring in the Australian-produced short series Brides of Christ (1991). She then co-starred in the 1992 TV miniseries Seekers alongside Josette Simon, produced by Sarah Lawson.
Buoyed by her Oscar win, Fricker went on to appear in several high-profile Hollywood films, most notably in Home Alone 2: Lost in New York as the Central Park Pigeon Lady (arguably her most popular film role). The following year she portrayed May Mackenzie (the Weekly World News-obsessed Scottish mother of Mike Myers' Charlie Mackenzie) in So I Married an Axe Murderer, and next portrayed Joseph Gordon Levitt's character's motherly caretaker Maggie in Angels in the Outfield. One of her last Hollywood film roles came with A Time to Kill, as Ethel Twitty (loyal secretary to Matthew McConaughey's Jake Brigance), after which she focused almost exclusively on film and television work in Canada and the British Isles. In 2003, she played Bernie Guerin, mother of Veronica Guerin (played by Cate Blanchett) in the film of the same name. She then played nurse Eileen in the film Inside I'm Dancing. In 2007, she starred in How About You the film based on a short story about people living in a residential nursing home written by Maeve Binchy, playing Heather Nightangle. Other important roles were Omagh in 2004 as police Ombudsman Nuala O' Loan, as Graiine McFadden in the TV docudrama No Tears about the women treated with the blood product Anti D in the seventies who had been contaminated with Hepatitis C, and as Aunt Maeve in Durango in 1999, based on the novel by John B Keane.
Fricker has appeared in Closing the Ring, Richard Attenborough's post-Second World War drama, also starring Shirley MacLaine, Christopher Plummer and Mischa Barton. in 2012 a high-profile supporting role in Albert Nobbs earned Fricker an Irish Film Award nomination, and along with Olympia Dukakis she became half of the first pair of Oscar-winning actors to play a same-sex couple in Cloudburst, a cultural milestone for the LGBT community that won awards worldwide
Fricker currently lives in the Liberties in Dublin. She was previously married to director Barry Davies. She says that her loves include her pet dogs, drinking Guinness, reading poetry and playing snooker. (She once stated that she had taken on the whole crew of My Left Foot. "I played pool against 17 of them, and beat them all," Brenda said)."If you're doing a scene and you think you're doing it wrong, just swear in the middle of it and then the director can't use it. It's an arrogant way of doing it, but unfortunately it's the only way of self-protection. You have to be a bit anarchic sometimes."
"When you are lying drunk at the airport, you're Irish. When you win an Oscar, you're British."
(on her character in Casualty) "Megan was the mother we all want, full of love and understanding. I'm none of that – I'm not a mother and never will be and I wasn't even a very good wife; I'm not even a good nurse to my father, now he's old and frail. I'm much more rebellious than Megan. I couldn't do her job ever. Just go down to the hospital and watch what they do for an eighth of the salary I earned pretending to be a nurse. It makes you blush. You break your heart with people being kicked in the teeth by life. I couldn't handle it. I'd be reduced to tears."
"Of all the films I’ve made, only three do I remember where I felt I’d moved forward as an actress: Cloudburst, My Left Foot and The Field."
At the National Theatre
The Plough and the Stars
At the Royal Court Theatre
Within Two Shadows
A Pagan's Place
At the Geffen Playhouse
Cat on a Hot Tin Roof
The Accrington Pals
The Irish Play
The Weeping of Angels