Born in Loftus, Sydney, he began performing as a stand-up comedian in 1989 at the age of 19 and, since 1997, has produced ten solo shows which have toured internationally.

[8][9] When researching his ancestry for the SBS television show Who Do You Think You Are?, broadcast on 2 April 2013, Hills found that several generations of his ancestors had been German burghers in what was then Sankt Sebastiansberg in Austrian Bohemia (now Hora Svatého Šebestiána in the Czech Republic), with his great-grandfather naturalising as an Australian citizen shortly after the start of World War I.

[16] He first became involved with The Children's Trust when he visited the charity in 2014 to meet Seb, a nine-year-old boy who had a severe brain injury and leg amputation following a road traffic collision.

[20] Hills was appointed Member of the Order of the British Empire (MBE) in the 2022 New Year Honours for services to Paralympic sport and disability awareness.

"[28] The phrase quickly became an audience chant, and Hills promised he would make it the name of his next show because, he says, "it was such an uplifting and genuinely silly moment.

It also appeared in a Detroit newspaper, on a Swedish website, and was yelled by Senator Natasha Stott Despoja in the Australian Parliament.

However, he had been performing live comedy for over a decade before he made reference to his prosthesis on stage, and it was only after "Go You Big Red Fire Engine" was nominated for a Perrier Award in 2001 that he began incorporating it into his act.

[4] Some of his influences include Chris Addison, Greg Fleet, Rich Hall, Daniel Kitson, Ross Noble and David O'Doherty.

In late-2007, he joined the show on a national live tour dubbed the "Spicks and Speck-tacular", with appearances in Melbourne, Sydney, Brisbane, Adelaide, Newcastle and Perth.

[33] In late 2011 and early 2012, the show hit the road again for Spicks and Speck-tacular – The Finale, appearing in Sydney, Newcastle, Brisbane, Gold Coast, Wollongong, Canberra, Adelaide, Perth and Melbourne.

[42] In 2012, he was part of the UK Channel 4 TV commentary team for the London 2012 Summer Paralympics,[43] and hosted a daily alternative review of each day's events, The Last Leg with Adam Hills, with Alex Brooker and comedian Josh Widdicombe.

In 2014, Hills returned to present four more celebrity specials; a full daytime series was hosted by Danish-born comedian Sandi Toksvig.

[47] In 2014, Hills co-starred in Die on Your Feet, an Australian TV series starring several real-life comedians as fictional comics at the Melbourne International Comedy Festival.

[53] In 2019, Adam Hills: Take His Legs was released, a sports documentary that follows the birth of the Warrington Wolves physical disability rugby league team from its creation, to the first PDRL World Club Challenge.

In August 2023, a sequel documentary about the inaugural PDRL World Cup was released, titled Adam Hills: Grow Another Foot.

[55] In March 2023, Hills partnered with Scott Hallsworth to open a permanent Freak Scene restaurant in Parsons Green in London.