Sampson was born in Sydney, Australia, and was educated at The Armidale School in northern New South Wales. He graduated from the AWARD School in 2002.
Sampson has had a diverse and distinct array of film roles, including Mad Max: Fury Road, Now Add Honey, Insidious, Insidious: Chapter 2, The Mule, Summer Coda, Darkness Falls, Razor Eaters, Kokoda, and Footy Legends. He was the suit actor for the role of Bull in Spike Jonze's Where The Wild Things Are.
Sampson was a special guest juror at the 2006 Melbourne International Film Festival, and host of the 2010 IF Awards, broadcast on SBS TV.
In 2010 Sampson helped his friend Leigh Whannell develop an Australian "paranormal chiller" called Insidious. Saw horror-writer Whannell, and Sampson are both former Recovery presenters. Insidious (previously called Vultures) first screened in September 2010 with Whannell and Sampson playing "comical low-tech paranormal investigators" Specks and Tucker.
Sampson's acting career launched in 1996 with role as Dylan Lewis's balaclaved sidekick "The Enforcer" on Recovery, an ABC youth music show. Later television jobs include roles on The Secret Life of Us, The 10:30 Slot, He also appeared as Effie's cousin Dimi in Greeks on the Roof, and as Ali in an episode of Stingers.
Sampson was a popular performer and series winner on the improvised Thank God You're Here (Series: 1, 2, 3, & 4).
In 2007, Sampson portrayed television personality Ugly Dave Gray in the television movie The King which examines the life of Australian TV legend Graham Kennedy. In the same year he also appeared in Wilfred. In 2008 he played Leonardo da Vinci in the children's television series Time Trackers. Sampson portrayed Michael Thorneycroft in the three final episodes of Underbelly, the series based on Melbourne's gangland war, 1995–2004.
In 2012, he teamed up with Toby Schmitz reaching the semi-finals in Season 1 of the hilariously confusing Australian word game Randling, hosted by Andrew Denton on ABC1.
In 2015, Sampson acquired a role on the FX hit show Fargo, playing the character Bear Gerhardt.
Sampson was an occasional co-host of Australian radio show Get This with Tony Martin on Triple M. Sampson was a founding member of The Forbidden Fruit, an experimental troupe whose only performance was a risque interpretation of Mad Max 2 they performed on late night radio, in which Angus played The Lord Humungous, who turned out to be quite proficient with the jazz flute. Sampson has also been a presenter on RRR's Breakfasters program. In addition, Sampson was also the un-credited host of the cult classic late-night radio show The Lonely Hearts Club, a deadpan comedy series which ran on ABC Radio National in early 2011 in which Sampson appeared under the pseudonym Richard Silk.