The duo will play married couple Charlie and Nicola in Mr and Mrs Murder. The couple work as industrial cleaners by day, but team up to solve crimes in their spare time.
Actor and comedian Micallef said in a statement: "I've enjoyed working with Ten on Talkin' 'Bout Your Generation over the last four years and am looking forward to continuing our relationship with Mr and Mrs Murder."
Logie Award-winning actress Stewart is best known to Australian audiences for shows including Tangle and Offspring, and has previously worked with Micallef on SBS's satirical comedy show Newstopia.
Fremantle Media Australia will produce for Channel Ten, with Ian Hogg from the company adding: "This is an exciting new chapter in murder mystery drama, which brings together an acclaimed production and storytelling team, and two of our most respected actors - a winning combination."
Filming on Mr and Mrs Murder begins this September in Melbourne, with the show debuting next year.