After Lyon's performance in the 2010 Futures League Twenty20 in December for the Comets in Melbourne which South Australia's Twenty20 coach Darren Berry witnessed he was selected to play for the Southern Redbacks in the KFC Twenty20 Big Bash.

[15] Lyon signed to play in the inaugural season of the Big Bash League for the Adelaide Strikers.

[14] In May 2017 it was announced that Worcestershire had signed Lyon as a replacement for compatriot John Hastings, who was competing in the ICC Champions Trophy.

[16] On 15 November 2017, during the final moments of the Sheffield Shield match against Queensland at the Allan Border Field, Lyon was involved in a bizarre incident, burning a piece of toast in the dressing room and causing the smoke alarm to go off, which brought the fire services to the ground and stopped play for 30 minutes.

[20] In August 2023, the Melbourne Renegades announced they had signed Lyon on a three-year deal for the Big Bash League starting with the 2023/24 season.

[21] In November 2023 Lancashire County Cricket Club announced that they had signed Lyon as an overseas player for the 2024 domestic season.

[23] He took two wickets for Australia against the Sri Lanka Board XI in the three-day warm-up match at the Paikiasothy Saravanamuttu Stadium.

[24] Lyon made his Test debut against Sri Lanka at Galle on 31 August 2011, he had his Baggy Green cap presented to him by Greg Chappell.

[30] Former Australian off-spinner Ashley Mallett criticised Lyon's delivery method during the series, saying he had been bowling too wide on the crease.

In June 2015, Lyon took his 142nd Test wicket, passing Hugh Trumble to become the most prolific wicket-taker of all Australian off-spinners.

He achieved this feat during the first Test against Sri Lanka at the Pallekele Cricket Stadium by dismissing Dhananjaya de Silva.

[39] A Facebook campaign was started up for fans at the 2016 Boxing Day Test against Pakistan to yell "Nice, Garry!"

in unison after Lyon's third ball bowled; however, their attempts were replaced by cheering, as he took the wicket of Sami Aslam with his third delivery.

He achieved this feat during the first Test against Bangladesh at the Sher-e-Bangla National Cricket Stadium by dismissing Mehedi Hasan Miraz.

On 6 March 2018, Lyon was fined 15 per cent of his match fee for a breach of the ICC Code of Conduct during the first Test against South Africa in Durban.

[48] Lyon awarded the Men's Test Player of the Year at the Allan Border Medal ceremony by the CA in 2019.

[55] On 16 July 2020, Lyon was named in a 26-man preliminary squad of players to begin training ahead of a possible tour to England following the COVID-19 pandemic.

[56][57] On 14 August 2020, Cricket Australia confirmed that the fixtures would be taking place, with Lyon included in the touring party.

[60] On 2 March 2023, Lyon become the highest wicket-taker in the Border-Gavaskar Trophy during the second day of the third test in Indore with a total of 112 wickets.

[63] In the 2023 ICC World Test Championship Final, Lyon recorded figures of 1/19 and 4/41 as Australia defeated India by 209 runs.

Forming a 55 run partnership with Pat Cummins, Lyon helped Australia to an unlikely two wicket win, ending the match with 16 not out off of 28 deliveries.