Kirwan was born in Churchtown, Dublin, Ireland. Her father, Peter Kirwan, was an insurance broker, and her mother, Maureen O'Driscoll, was a language teacher. She is the youngest of three daughters. She attended Loreto Beaufort in Rathfarnham, Dublin, a Catholic school for girls, until the age of 16, when she was asked to leave as her career as an actress started to progress. Kirwan completed secondary school at the now-defunct non-denominational school Sandymount High School in Dublin.
One of Kirwan's great-grandfathers, Henry Kahn was a Polish Jewish immigrant who had married one of Kirwan's great-grandmothers, Teresa O'Shea, a Catholic, in Ireland. Kirwan is a great-granddaughter of Margaret Collins-O'Driscoll, who was a sister of Michael Collins, one of the Irish leaders during the Irish War of Independence. Kirwan's maternal grandfather Finian O'Driscoll was Michael Collins's nephew.
Kirwan's first credited TV roles were in the TV series Troubles in 1988 and The Lilac Bus in 1990 alongside Stephanie Beacham based on Maeve Binchy's novel.
At the age of sixteen Kirwan moved to London when she was cast in a play at the Bush Theatre. She won acclaim in 1988 for her performance as the factory girl Linda in A Handful of Stars, the Bush Theatre premiere of the first play in Billy Roche's Wexford Trilogy. In 1992, again at the Bush, she starred in a revival of the complete trilogy.
Her television breakthrough role was appearing in the 1991 BBC Scotland production of A Time To Dance, adapted by Melvyn Bragg from his own novel, playing Bernadette Kennedy. In the same year, she also appeared in the play Water Music at the Cockpit Theatre, written by award-winning playwright Lyndon Morgans (singer-songwriter with the Welsh folk noir band Songdog). In 1992, she also starred in Hush by April De Angelis at the Royal Court Theatre, while January 1994 found her playing in Peter Hall's seasonal production of Georges Feydeau's farce An Absolute Turkey at the Globe Theatre
Kirwan briefly appeared in Casualty, and in the first three series of Goodnight Sweetheart alongside Nicholas Lyndhurst. In 1997, she sang with Dustin the Turkey on his cover of "Fairytale of New York" for his album Faith of Our Feathers.
For 23 episodes, from 1996–1998, she appeared in Ballykissangel in the role of Assumpta Fitzgerald. Assumpta is the landlady of BallyK's only pub, Fitzgeralds, and is no friend of the church – until Father Peter Clifford (Stephen Tompkinson) is posted to the village from his previous parish in Manchester. She also continued this role for a Comic Relief special of The Vicar of Dibley, and in a Father Ted special. Kirwan 's performance in Ballykissangel won her the National TV Award for Best Actress in 1996, and the Irish Post Award for Best Irish Entertainer in 1997. In 1998, she starred alongside Christopher Eccleston in the Michael Winterbottom film With or Without You as Belfast girl Rosie Boyd.
In 1999, she appeared in another BBC production, a made for TV Christmas film called The Greatest Store in the World. She played the single mum of two girls who are made homeless a few days before Christmas. Kirwan co-starred with Brian Blessed and Peter Capaldi. In 2001, she starred as Emma Rose in a BBC series Hearts and Bones alongside Sarah Parish, Amanda Holden, Hugo Speer and Damian Lewis. The show ran for two series. She also starred in the Sky TV series The Bombmaker as a former IRA bomb maker. That year she also appeared in a stage production of Dangerous Corner by JB Priestley in Leeds alongside now husband Rupert Penry-Jones.
In 2003, Kirwan again appeared on stage with Penry-Jones in Les Liaisons Dangereuses at the Bristol Old Vic directed by Samuel West.
Kirwan starred in School for Seduction, a 2004 film which also starred Kelly Brook. She appeared in the BBC 1 crime drama series 55 Degrees North with Don Gilet, which aired in 2004. She returned for a second series in 2005. The series was shown in the US under the title The Night Detective. In 2005, she also appeared on the Lyttelton stage at the National Theatre in the role of Alice in Brian Friel's Aristocrats. In 2006, she played Bertha in Exiles at the National Theatre.
In 2007, she appeared in the BBC drama True Dare Kiss and on stage in Harold Pinter's Betrayal at the Donmar Warehouse.
Kirwan appeared as the villain Miss Hartigan in The Next Doctor, the 2008 Christmas special of Doctor Who, alongside David Tennant and David Morrissey.
In 2009, Kirwan was in the BBC drama Moving On, where she played Laura in the episode Dress To Impress. She also guest starred in Law & Order: UK, playing the role of Beatrice McArdle.
Kirwan appeared in the Irish film Ondine alongside Colin Farrell and Stephen Rea which was released in 2009. She played Maura, the alcoholic bitter ex-girlfriend of Farrell's character Syracuse. Kirwan won the award for Best Supporting Actress in a Film at the 2010 Irish Film and Television Awards (IFTAs) for her role in Ondine.
Kirwan appeared in the BBC drama series Material Girl, which aired in January 2010. She was also cast in the role of Bundle in Agatha Christie's Marple.
Kirwan also appeared in the four-part BBC drama The Silence in 2010. She played the role of the warm-hearted aunt of a young deaf girl who witnessed a murder. The Silence aired in July 2010. For her role as Maggie, Kirwan won the Dagger for Best Supporting Actress at the 2010 Crime Thriller Awards.
Kirwan has also been the subject of an episode of Who Do You Think You Are? in which she found out more about her Irish and distant Jewish descent. Her great uncle was the Irish nationalist leader, Michael Collins. It was first shown on 2 August 2010.
In 2011, Kirwan worked on Injustice a five-part psychological thriller on ITV written by Anthony Horowitz. She starred as Jane Travers, wife of main character, Will Travers played by James Purefoy.
From April to May 2012, Kirwan appeared on stage at the Chichester Festival Theatre in a Jeremy Herrin production of Uncle Vanya. Kirwan played Sonya alongside an exceptional cast which included Roger Allam (as Vanya), Timothy West and Lara Pulver. The play received warm reviews and response to Kirwan's performance was generally positive.
In June 2012, Kirwan appeared on screen as Alex Demoys alongside Christopher Eccleston in the three part BBC1 drama miniseries Blackout.
Other works in development include a fantasy film Luna and an independent thriller, Entity. Entity premiered in 2013 at selected cinemas and DVD and won Best Horror film at the London Independent Film Festival 2013.
In April 2013, Kirwan was cast as Valerie in Josie Rourke's revival of The Weir by Conor McPherson at the Donmar Warehouse. Kirwan appeared alongside Brian Cox, Ardal O'Hanlon, Risteard Cooper and Peter McDonald. Reviews for The Weir have been excellent with 4* and 5* ratings by top critics. The Weir later transferred to the West End, playing at Wyndham's Theatre from January 2014 to April 2014.
The film Luna by Dave McKean and starred Dervla, Ben Daniels, Stephanie Leonidas and Michael Maloney which began filming in 2007 but due to budget setbacks only completed filming in 2011 was finally completed in 2013 and premiered at the Toronto International Film Festival in 2014. The film warm positively received by critics and Dervla's performance was highly praised. Luna was awarded the Best British Film at the Raindance Film Festival.
In late 2014, Kirwan made her second stint at the Chichester Festival Theatre as Frankie in Frankie and Johnny in the Clair de Lune, a play by Terrence McNally about the relationship between waitress, Frankie and short-order cook, Johnny played by Neil Stuke. The play was well known for its extended nudity in the first Act. The play was also warmly received by critics who gave mostly 4* reviews. It ran from November 2014 to December 2014 at the Minerva theatre.
Dervla Kirwan has also branched out to producing, taking on the role as an associate producer of an independent film, Silent Hours which as of April 2015, is currently in post-production.
In 2016 she starred as the violent and cruel crime boss Ed in Branko Tomovic's directorial debut Red and received a Best Supporting Actress nomination at the Maverick Movie Awards 2016. She also won the Best Actress Award at the Flagship City International Film Festival 2017 for this.
Kirwan is married to actor Rupert Penry-Jones, with whom she has two children, Florence and Peter. She met him in 2001 while appearing in Dangerous Corner and they married in 2007 after a three-year engagement. She had previously been engaged to Stephen Tompkinson, her co-star in Ballykissangel, in 1998.
She and Penry-Jones both appeared in Casanova in 2005, although they did not share any scenes. They had worked on stage together in 2001 in a West Yorkshire Playhouse, Leeds, production of J B Priestley's Dangerous Corner, when he played Robert Caplan to her Olwen Peel.