Stewart has won acclaim on-stage in a range of dramatic and comedic roles. As an ensemble member of Red Stitch Actors Theatre from 2002–12 Stewart appeared in over a dozen plays for the company including The Little Dog Laughed, The Shape of Things, Rabbit Hole, Bug, Dirty Butterfly, Play About the Baby and Loyal Women. Her final Red Stitch production was in December 2010 in the part of Tekla in an update of August Strindberg's Creditors.

For her theatrical work, Stewart has twice won and twice been nominated for Green Room Awards. In 2004, she won the Gerda Nicolson Award (for an Emerging Actress) and in 2006 won Best Actress for Bug/The Shape of Things. She was nominated as Best Actress for her body of work in 2003 and again as Best Actress for the Red Stitch production of The Little Dog Laughed in 2008.

Stewart was nominated for the Graham Kennedy Award for Most Outstanding New Talent at the Logie Awards in 2006 and two ASTRA awards in 2006 and 2007 for her role in the comedy series Supernova. She won acclaim for her role as Roberta Williams in Underbelly, winning an AFI award for Best Lead Actress in a Television Drama and being nominated for two Logies in 2009, winning the Silver Logie for Most Outstanding Actress. In 2010 she was nominated again for the Silver Logie for Most Outstanding Actress, this time for Tangle, and an ASTRA award for :30 Seconds. Stewart was rewarded for her work as Billie Proudman in Offspring by winning Best Guest or Supporting Actress in a Television Drama at the 2014 AACTA Awards, a nomination for Best Lead Actress in a Television Drama at the 2015 AACTA Awards and nominations for the Silver Logie for Most Outstanding Actress in 2011, 2012 and again in 2014. The cast of Offspring were also acknowledged with nominations for the Equity Awards for Outstanding Performance by an Ensemble in a Drama Series for 5 years running from 2011 to 2015 and again in 2017.

It was her award-winning performance in Underbelly in 2008 that first made Stewart a household name. The portrayal of Roberta Williams drew praise from critics including Marcus Casey of ‘The Daily Telegraph’, who described it as 'one of the most compelling performances by an Australian Actress in memory.' Casey expanded that it was ‘a brutally brave, ugly and compelling performance...She held nothing back, and was an emotional but controlled and screeching tornado who dominated the screen whenever the camera peered her way.' The authenticity of Stewart’s performance was praised by Michael Lallo in ‘The Age’, ‘By any measure, it's the role of a lifetime. Stewart has ensured it's the standout performance of the series. Despite quality performances by all, critics say she owns every frame she's in. It's not that she delivers a superb depiction of a suburban gangster moll; it's that you really believe she is a suburban gangster moll.’ Although her performance was popular with critics and audiences, the real life Roberta was not a fan but Stewart was sympathetic, "Obviously, I would have preferred her to like it," she said. "But I can't control that. And if someone was playing me, I couldn't imagine I'd be happy…I have a lot of empathy for Roberta and what she's been through.” Stewart acknowledges the show was a key moment in her career, "Underbelly opened a lot of doors and gave me access to better opportunities and more opportunities. I am very grateful for it.” Despite her positive experience in Underbelly, Kat Stewart chose not to reprise the role in Fat Tony & Co in 2014. Stewart told David Knox of 'TV Tonight': “..Seven years ago when I did it we didn’t know much about Roberta Williams. So I did as much research as I could...Now we know how she walks and talks and so much more about her...I don’t like turning down work. It goes against every actor instinct. But it just didn’t feel right.”

After the success of Underbelly Stewart next appeared in the critically acclaimed relationship drama, Tangle (2009–2012) on Showcase. In the series Stewart played the loveable but flawed, Nat Manning alongside Justine Clarke, Ben Mendelsohn, Matt Day and Catherine McClements. Showing she has long been adroit at both drama and comedy, in 2009 Stewart appeared in the Andrew Denton produced, advertising industry satire :30 Seconds on Comedy Channel.

Stewart married fellow actor David Whiteley in Melbourne in February 2008. The couple met while working at Red Stitch Actors Theatre in 2002. Their first child, a boy named Archie Nicholas, was born on 12 January 2012. The actors share parenting duties between work commitments, "The great thing about this profession is it’s a period of intense work but you have great breaks as well. We co-parent; it’s 100 per cent a team effort. We also have parents who are besotted with Archie," Stewart said in 2014.

In 2013 Stewart teamed with Shaun Micallef in the murder mystery drama/comedy, Mr & Mrs Murder on the Ten Network. The pair played Charlie and Nicola Buchanan, a husband and wife duo of industrial cleaners with an amateur interest in solving crimes. The two previously worked together on the satirical SBS newscast show Newstopia and both have spoken positively of their on-screen chemistry and rapport with Micallef saying "I wouldn't have considered doing this if Kat wasn't involved." Stewart also shared an Associate Producer credit on the show.

Stewart was part of the judging panel at the Tropfest Australia 2014 Short Film Festival. In 2014 Stewart also starred in the Matt Holcomb directed short film, Flat Daddy. The production was nominated for Best Short Fiction Film at the 2015 AACTA Awards.

Stewart and Whiteley welcomed a second child, a daughter named Georgia Kitty (known as Gigi) born on 16 March 2016. Stewart embraces being a working mother. "There's a lot of muddling", Stewart explained in June 2017. "I think if we had standard corporate jobs it would be very different. There's no great secret, it's really just luck and flukes. And sometimes it's chaos when we're both working at once."

Kat Stewart's other TV credits include guest appearances in the real-life comedy series True Story with Hamish & Andy on the Nine Network in 2017, No Activity on Stan in 2015, It's a Date and Jack Irish: Dead Point in 2014, Camp on America's NBC in 2013, Miss Fisher's Murder Mysteries in 2012, various roles in Newstopia on SBS in 2007-08, the BBC2/UKTV comedy series Supernova, as well as recurring roles on City Homicide, Kick, and Last Man Standing. Earlier in her career Stewart had guest roles on Blue Heelers, Stingers, CrashBurn, Something in the Air, The Secret Life of Us, and Fergus McPhail. In 2015 Kat Stewart appeared with close friend and mentor Ailsa Piper in the contemporary interview program 'The Truth About Us' on Foxtel's Bio. channel.

Stewart won many new fans in her role as Billie Proudman on Offspring, as part of an ensemble cast led by Asher Keddie and including John Waters, Eddie Perfect, Deborah Mailman, Richard Davies, Garry McDonald, Lachy Hulme and Linda Cropper. One of the show's strengths is the dynamic relationship between the sisters Billie and Nina Proudman (played by Keddie). Both actresses have spoken of their admiration for each other, with Stewart saying "I've admired Asher ever since Love My Way. She is an Actress of extraordinary ability and depth. We have a lovely shorthand and support for each other on set, not unlike Nina and Billie. There's a trust there that allows real spontaneity and joy." Keddie spoke of Kat, saying "It's exhilarating to perform with her; I feel genuinely excited by it. That's a great feeling to have as an actor - when you really want to be working opposite someone and with someone. It doesn't get much more rewarding than that." Stewart admits to being fond of her character, Billie, despite some heartaches, "I’m really fond of her, though she’s really frustrating sometimes. Though she cheated on Mick [in season four], it’s my job to see the world through her eyes. You see what happened in the lead-up and it was the ultimate act of self-destruction. It broke my heart." Offspring aired for 5 seasons from 2010–14 before returning to TV screens for a sixth season in 2016. With production of the new series underway Stewart spoke to Colin Vickery of News Corp, "I really didn’t think it would happen", Stewart said. "It was the best experience I’ve had in a show. You form such deep relationships with the people and also the characters. I feel really confident we’ll be able to deliver something great. I don’t think we’re going to coast on some sort of legacy. We’re really aware of that and all want it to be as fantastic and awesome as it can be. To get to walk around in Billie’s shoes again is fantastic.” The seventh season of the show, including Stewart and other key cast members, screened in 2017. Writing in 'The Daily Telegraph', Colin Vickery reflected on season 7 with 'this year...Billie, played by Kat Stewart, has had to endure a heartbreaking split with husband Mick (Eddie Perfect). Billie’s rollercoaster life has showcased Stewart’s comedic and dramatic talents like never before. No wonder many critics believe she is the best actor on Australian television.' No decision has yet been made on whether the show will return for an 8th season.