"[8] He attended Durham University, where he studied philosophy and met fellow comedians Nish Kumar, Nick Mohammed and Tom Neenan.

He performed with Peacock at the Edinburgh Festival Fringe in 2011, 2012 and 2013, as well as supporting Greg Davies on his successful Firing Cheeseballs at a Dog Tour in 2011.

His stand-up performances contain much observational comedy, often aimed at himself, including discussion of his Type 1 diabetes, which he was diagnosed with as a thirteen year old; he chose that as the central topic of his 2018 Edinburgh Fringe show Blizzard[11] and his Amazon Prime Video special Blood Sugar.

In the same year, he appeared with Amy Hoggart in Almost Royal, a faux-reality show on BBC America, where the two portrayed siblings Georgie and Poppy Carlton.

[16] In May 2022, Gamble was announced as one of six rotating co-hosts joining Alexander Armstrong on Pointless to replace Richard Osman, alongside Sally Lindsay, Konnie Huq, Lauren Laverne, Alex Brooker and Stephen Mangan.

[17] Gamble appeared with Acaster on the fifth series of Celebrity Hunted (2023), which tasked participants with evading "Hunters" around the UK for a fortnight.

During their appearance they ate in a Michelin starred restaurant,[18] called into Gamble's Radio X programme,[19] and released a video mocking the Hunters.

[25] In October 2023, Gamble published his debut book, titled Glutton: The Multi-Course Life Of A Very Greedy Boy, an autobiography focused through his lifelong obsession with food.

[11][27] Gamble married TV producer and member of Supermilk Charlie Jamison on 9 September 2021, after postponing three times due to the COVID-19 pandemic.