[3][12] In the following years, Coughlan did voice work in animated series and films, including The Fairytales from 2004 to 2005, Summer of the Flying Saucer in 2008, Simsala Grimm II: The Adventures of Yoyo and Doc Croc in 2010, Thor: Legend of the Magical Hammer in 2011, and Ivan the Incredible in 2012.

[18] Derry Girls is Channel 4's most successful comedy since Father Ted,[19][20] and the most watched show in Northern Ireland since modern records began in 2002.

[24] Though Derry Girls was broadcast in January and February 2018 on Channel 4, it was after its rerelease onto Netflix in December that same year that the show gained international audience and popularity.

[34] Coughlan played Penelope Featherington, a reluctant debutante and youngest daughter of a nouveau-riche family in Regency era London.

[12][35] Coughlan's role was significantly cut back in the third series of Derry Girls in 2022 due to scheduling conflicts with Bridgerton and the coronavirus pandemic.

[54] Coughlan starred alongside Lydia West in Channel 4 sitcom Big Mood, a six-part dramedy series about two best friends navigating friendship amidst a mental health crisis.

[55][56] Big Mood was Channel 4’s most-watched new comedy launch since Derry Girls,[57] and Coughlan received praise for her role as Maggie Donovan.

[57] Coughlan then starred as Humble Joan alongside Aimee Lou Wood and Lolly Adefope in Seize Them!, a 2024 comedy film set in the Dark Ages.

[74] Coughlan will play the role of Silky in the upcoming adaptation of Enid Blyton‘s The Magic Faraway Tree, alongside Andrew Garfield, Claire Foy and Rebecca Ferguson.

[77] Coughlan has narrated several audiobooks, including Sense and Sensibility by Jane Austen,[78] Big Girl, Small Town (abridged) by Michelle Gallen,[79] The Temple House Vanishing by Rachel Donohue,[80] Listening Still by Anne Griffin, [81] and an Audible Original, Misdirected by Lucy Parker, alongside Gwilym Lee.

[86] She also narrated a chapter of Meet the Georgians: Epic Tales from Britain's Wildest Century by Robert Peal alongside Bridgerton co-star Adjoah Andoh,[87] and she appeared in a cameo role as Countess Christiana in That Friend by Sabrina Brier.

[89][90] In 2021, along with Big Mood creator and writer, Camilla Whitehill, Coughlan co-created, co-wrote and starred in Whistle Through the Shamrocks, a six-episode scripted comedy podcast with a star-studded cast, including Ben Miller, Louisa Harland, Stephanie Beatriz and Jonathan Van Ness.

[95] Per McGrath: “Brave, bold and beautiful, Nicola embodies inspirational individuality, sophisticated strength and an independent spirit – I can truly say she is the Belle of the Ball!”[95] In October 2023, Coughlan partnered with Uber Eats Australia for its campaign to help address period poverty.

"[105] In October 2017, in a now-deleted tweet, Coughlan shared that she had been teen-aged when she was told by an "older, respected director" that if she wanted to impress him in an acting competition, she should perform naked.

"[106] In 2018, while Coughlan was appearing on stage in The Prime of Miss Jean Brodie at London's Donmar Warehouse, she wrote a piece for the Guardian calling out the unfair scrutiny of women's bodies common in theatre criticism.

"[110][111][112] In the same month, Coughlan rebuffed claims by Internet trolls that Bridgerton photoshopped her waist, clarifying, “If you wear corsetry for long enough, your body really molds to it.

"[113][114] In February 2019, 28 women with their suitcases led by Coughlan crossed London's Westminster Bridge to demand the decriminalization of abortion in Northern Ireland.

[120] On 12 April 2022 upon the release of the third series of Derry Girls, Coughlan protested the attempted privatisation of Channel 4, posting a picture of herself holding up a middle finger on Instagram and linking to a change.org petition.

[123][124] Coughlan was one of over two thousand to sign an Artists for Palestine letter calling for a ceasefire and accusing Western governments of "not only tolerating war crimes but aiding and abetting them.

[126] On 9 October, 2024, in her speech as a TIME100 Next honoree, Coughlan called for the U.S. and UK to “stop sending arms to Israel, to release the hostages, [and] to send aid into Gaza.”[127] In December 2024, Coughlan partnered up with HURR and Choose Love to rent out a selection of her wardrobe, with proceeds going to Choose Love, a UK-based charity supporting refugees and displaced people all over the world.