He is known for his creation and portrayal of several characters in the mockumentary television series We Can Be Heroes: Finding The Australian of the Year (2005), Summer Heights High (2007), Angry Boys (2011), Ja'mie: Private School Girl (2013), Jonah from Tonga (2014), and Lunatics (2019).

He began his career in his twenties as a stand-up comedian while also working as a childcare worker at Turramurra North Public School and a shop assistant.

In 2015, Lilley was the main actor for The Stafford Brothers, Rick Ross and Jay Sean's "When You Feel This" music video.

[4] Lilley portrayed several characters in the series: Phil Olivetti, a self-obsessed police officer; Ricky Wong, a Chinese Australian university physics student from Melbourne; Pat Mullins, a 47-year-old housewife with a dream to roll on her side from Perth, Western Australia to Uluru, Northern Territory; Daniel Sims, a teenage boy who donates an eardrum to his deaf twin brother, Nathan (both Daniel and Nathan later appeared in "Angry Boys"); and Ja'mie King, a narcissistic girl attending a private high school in Sydney (Ja'mie later appeared in "Summer Heights High" and "Ja'mie: Private School Girl").

It was produced by Melbourne-based production company Princess Pictures and Chris Lilley, and was a co-production between the ABC in Australia and HBO in the US.

Lunatics features six different characters, all played by Lilley, which include fashion retailer Keith Dick; estate agent Quentin Cook; 7-foot college student Becky Douglas; 12-year-old Gavin McGregor, who is an heir to an earldom; ex-pornstar Joyce Jeffries; and South African Jana Melhoopen-Jonks, a celebrity pet psychic who is also a lesbian.

[25] Lilley collaborated with The Jonas Brothers and Paris Hilton with his Lunatics characters Keith Dick and Jana Melhoopen-Jonks.

[29] Lilley's series Summer Heights High gained significant controversy, criticism and media scrutiny for its portrayal of such issues as mental disabilities, homosexuality, sexual abuse, and racism.

[30] The Herald Sun reported that parents and some teachers have considered the possibility that the show is influencing children to misbehave at school.

[30] ABC apologised to the family, stating that the situation was purely coincidental and assured them that the filming of the episode in question had been completed eleven days before her daughter's death.

On 24 July 2017, the court case based on the death of Elijah Doughty had ended in controversy and was the subject of pro-Aboriginal protests.

[36][37][38] The creators of the 2004 ABC TV documentary series Our Boys stated that Lilley drew inspiration for the Jonah character from their work.

[39] The subject of Our Boys recalled being "absolutely embarrassed, full of hate, angry and exploited" by the "racist" Jonah character that was based on him.

"[43] Following the 2020 Black Lives Matter protests, BBC iPlayer removed Jonah from Tonga from its online streaming service.

[44] On 11 June 2020, Netflix confirmed it had removed four of Lilley's series from its streaming service, also in response to the Black Lives Matter protests and movement.

[45] In the weeks following these events, Lilley posted multiple videos of content involving the Jonah character to his YouTube channel.