Born in Lambeth, South London, Luke’s career began with Arsenal at the age of eight. 

He won the Premier Academy League and FA Youth Cup double with the Gunners in 2008/09, partnered in defence with centre-back Kyle Bartley, now of West Brom. Jack Wilshere, Henri Lansbury and James Shea were also among that squad. 

After an initial loan spell with Yeovil Town in League One, where Luke made his professional debut, the switch was made permanent in the summer of 2010. 

Luke became a mainstay for the Glovers and played in the 2012/13 play-off final as Yeovil beat Brentford 2-1 to earn promotion to the Championship for the first time in the club’s history. Future Newcastle United defender Dan Burn was also on the Yeovil teamsheet, while Toumani Diagouraga - now an Academy coach at Boro - and Luke’s future Leeds teammate Adam Forshaw played for Brentford.

In July 2014, Luke signed a three-year deal at Bristol City, and in his first season at Ashton Gate won the Football League Trophy after a 2-0 victory over Walsall at Wembley. Also playing for City that day was Aden Flint, while George Saville was a substitute. 

Bristol City were League One champions that season with Luke playing a total of 58 matches, while he was a key cog the following campaign too as the Robins cemented their second-tier status. 

Luke signed for Leeds in August 2016 following a recommendation to their boss Garry Monk from former Arsenal teammate Bartley, who was on loan at Elland Road.

Narrowly missing out on the play-offs that season, it was nevertheless something of a turning point for Leeds following years in the doldrums, and Ayling quickly became a fan favourite.  

In the 2018/19 season, Leeds appointed Marcelo Bielsa as head coach. That campaign, Luke reached the milestone of 100 appearances in a United shirt and also began deputising for Liam Cooper as captain. The club’s promotion hopes were halted by Derby County in the play-offs. 

In December 2019, Luke was named in the Guardian’s Football League Team of the Decade.

In 2019/20, Leeds were once more looking like a force for promotion, and despite a pause in the season due to COVID-19 finished the job in July when they were crowned champions of the Championship.

Luke was awarded 2019/20 Fans’ Player of the Year, and won Leeds’ Goal of the Season award for a sweet volley against fierce Yorkshire rivals Huddersfield Town.

Luke made his Premier League debut in the first match of the following season, a 4-3 defeat to reigning champions Liverpool at Anfield. He featured in all 38 top-flight matches for Leeds in 2020/21. 

Remaining a regular for Leeds in the Premier League, Luke made his 250th appearance for the club in May 2023 against Newcastle. He also scored his first Elland Road goal in the top flight, but the 2-2 draw edged Leeds - by this point managed by Sam Allardyce - closer to the Premier League trapdoor.

Following relegation in May 2023, Luke made 16 appearances for the Yorkshire side in the Championship, scoring once in a 1-1 draw with West Brom.

He joined Boro on loan in January 2024 on a short-term deal until the end of the campaign.

Luke quickly established himself as an important figure in the Boro team. He tallied up eight assists in 19 appearances.

Luke then made his move permanent ahead of the 2024/25 season when he signed a two-year contract at the Riverside.