In addition to cricket, Duffin has played Australian rules football for Collingwood, North Melbourne, and Hawthorn in the AFL Women's competition.

She has also received recognition for her outstanding performance at state league level, winning the 2018 Lambert–Pearce Medal while playing as a midfielder for Williamstown in the VFL Women's competition.

Born in the Melbourne suburb of Williamstown,[2] Duffin has described her childhood as "really sporty" and that "growing up with an older brother and my Dad meant I was in the backyard a lot... pretty much playing AFL and cricket from the age of four".

[3] After receiving encouragement by a school teacher, she attended an under-12 cricket training camp that resulted in selection for Victoria at junior level.

[15] In a low-scoring final against New Zealand, Duffin put on a 30-run partnership with Leah Poulton to help Australia win by three runs and claim their maiden World Twenty20 championship.

[17] In an ODI against India on 16 March 2012 at Wankhede Stadium, Duffin recorded her highest score at international level, making 90 not out off 87 balls which steered Australia to a five-wicket win.

[23] On 11 August 2013, Duffin recorded her maiden Test half-century during a drawn Women's Ashes match at the Sir Paul Getty's Ground.

[25] Duffin's best performance at the 2014 World Twenty20, held in Bangladesh, came against South Africa when she scored 27 not out off 24 deliveries and put on an unbeaten 60-run stand with Ellyse Perry.

[30] In December 2019, during and after an outstanding WBBL|05 season, media speculation mounted around Duffin's potential recall to the national team ahead of the 2020 Women's T20 World Cup.

[31][32][33][34][35] However, she declined to participate in an upcoming Australia A series against India A, which some outlets interpreted to mean she had chosen to prioritise her AFL Women's career.

[36][37] In actuality, she had decided to prioritise starting a family with her husband Chris, announcing on 31 December she would halt her dual-sporting commitments to give birth to the couple's first child.

[38][39][40] At the age of 17, Duffin made her senior debut for Victoria in the Women's National Cricket League (WNCL) and played all eleven of the team's games for the 2006–07 season.

[50] At the official Women's Big Bash League (WBBL) launch on 10 July 2015, Duffin was unveiled as the first-ever player signing for the Perth Scorchers.

[30] In June 2016, a month after Duffin signalled a return to top-level domestic cricket, the Melbourne Stars announced they had "won the race for the prized signature of the former Australian batter" by recruiting her for the WBBL|02 season.

[59] Among her highlights was an unbeaten 27-ball innings of 50 runs on 27 November 2019 against the Brisbane Heat, helping the Renegades mow down a target of 184 and set a new league record for the highest successful chase.

[62] Three months after giving birth to her first child, Duffin withdrew from the 2020–21 Women's Big Bash League season, saying her body was not yet ready for a return to the cricket field: "I've always prided myself on my preparation and there just hasn't been that opportunity this year.

"[63] Even while a member of the Australian cricket team, Duffin occasionally played football with various clubs including Melbourne University, Wyndhamvale and St Kilda Sharks.

[69][70] On 3 September 2016, she played in another exhibition match for Melbourne—this time an All-Star clash against the Western Bulldogs at Whitten Oval, with the two teams made up of the best female players nation-wide.

[73] On 3 February 2017, she made her debut in the opening match of the league's inaugural season, which resulted in a 35-point loss to Carlton at IKON Park.

[76] Due to an adductor injury, Duffin had a delayed start to the 2018 AFLW season,[77] playing her first game of the year in a 13-point round two loss to Fremantle at Optus Stadium.

[78] In round six, she recorded her first League B&F votes, picking up 18 disposals in a 14-point win against Brisbane at Moreton Bay Sports Complex and being adjudged second-best on ground.

[84] Despite having the third-best record in the league, North Melbourne controversially failed to qualify for the four-team finals series due to the competition's conference structure.

[40] Following a 714-day absence, Duffin made her AFLW return in round five of the 2021 season, registering eleven disposals and five marks in a 22-point defeat of Carlton at UTAS Stadium.

[63] In addition to conventional nicknames such as "Duff" and "Camo",[95][96] Duffin is often referred to as "Soggy" or "Sog" on account of one particular cricket training escapade in which she waded through a nearby flowing creek to retrieve a misdirected ball.