Parkinson's early roles were small parts in long-running British television series such as Dalziel and Pascoe, The Bill, and Holby City. He made his film debut in 2007 in Control, a biopic of Joy Division singer Ian Curtis in which he played the role of Tony Wilson. In 2008 he starred in the British independent film The Taxidermist, playing The Taxidermist. The film won several awards, including Palm Springs International Short Film Festival 'Best Live Action Film over 15 minutes' and Rhode Island International Horror Film Festival 'Best Short Film'.
In 2009 he played the abusive care worker Ben in the British television drama The Unloved, the directorial debut of Samantha Morton. Parkinson had previously starred alongside her in Control. The Unloved also featured Lauren Socha, with whom Parkinson would later star alongside in Misfits, as well as his wife, Susan Lynch.
In 2010 Parkinson played both of the twins Jimmy and Johnny Kray in the ITV television series Whitechapel. The role involved a boxing scene which he prepared for by taking boxing lessons and going on a no-carb diet. In the same year he played Alan in the British film SoulBoy and Cubitt in the British film Brighton Rock. Towards the end of 2010 he began playing the probation worker Shaun in the E4 television series Misfits. He continued this role throughout 2011.
In 2011 Parkinson appeared as the corrupt DS Matt 'Dot' Cottan in the award-winning BBC Two series Line of Duty.
In 2012 he appeared as the Reverend Horace in the BBC supernatural thriller The Secret of Crickley Hall, adapted from the novel of the same name written by British author James Herbert. The Secret of Crickley Hall also featured his wife. Parkinson also starred in the music video for the song "Two Fingers" by Jake Bugg.
He reprised his role as Matt 'Dot' Cottan in 2013 for the second series of Line of Duty, and in 2015 for the third series.
In 2015, he originated the role of Inspector Fry in Martin McDonagh's acclaimed play Hangmen, which premiered at the Royal Court Theatre before transferring to London's West End after a sold-out run, and being broadcast by National Theatre Live. He also played the compassionate missionary Dougie Raworth in Indian Summers.
In 2017, he appeared on the UK panel show Would I Lie to You?.
