He is known for his energetic physical comedy routines, telling stories accompanied with mime, and sound effects[3] of things such as machinery and animals.

[7] He has appeared in films such as Yes Man (2008), The Boat That Rocked (2009), Love Birds (2011), What We Do in the Shadows (2014), Trolls (2016), Jumanji: Welcome to the Jungle (2017), Guns Akimbo (2019), Relax, I'm from the Future (2022), Uproar (2023) and Next Goal Wins (2023).

From March 2022 to October 2023, he starred as Stede Bonnet alongside Taika Waititi in the HBO Max period romantic comedy series Our Flag Means Death.

[11] After winning an open mic contest at Southern Blues Bar in Christchurch, the duo began performing at local venues.

[12] Rhysently Granted performed at two international comedy festivals which led to Darby moving back to Auckland to seek more solo stand-up experience.

[13] After performing his first solo show at the 2002 Edinburgh Festival Fringe, Darby moved to the UK to pursue his career further.

[5] In 2004, he appeared in the Flight of the Conchords BBC radio series as the band's manager Brian Nesbit alongside comedy stars such as Rob Brydon, Andy Parsons and Jimmy Carr.

Rhys Darby's hair colour is self-described as Electric Copper in the episode of Flight of the Conchords entitled Murray Takes It to the Next Level.

Darby played the role of Angus in the Richard Curtis film The Boat That Rocked[19] released in the UK on 1 April 2009.

On 10 August 2010, Entertainment Weekly claimed that Darby was in consideration for a role in the television series The Office after Steve Carell left at the end of the 2011 season; however, this did not materialise.

[28] Darby climbed to the summit of Mount Kilimanjaro in July 2013 as part of a World Vision team of celebrities that included Olympian Mahé Drysdale and musician Boh Runga.

On 8 November 2013, Darby made an appearance and performed some standup comedy in his capacity as second guest on the Late Show with David Letterman.

The series received critical acclaim for its LGBTQ representation,[32] in part due to the romantic relationship between Bonnet and Blackbeard, played by co-star Taika Waititi.