In 2006 and in his home town of Melbourne, Targett competed in the 50-metre butterfly, finishing second and placing above more experienced countrymen Michael Klim and Matt Welsh.

Targett's second international meet was at the 2008 Olympics in Beijing, China, capturing a silver in the 4×100-metre medley and a bronze in the 4×100-metre freestyle relay, both in new Commonwealth record time.

[1] Matt Targett's first world championships came in 2009 in Rome, Italy, he swam 4 races on day one, and thus not looking in peak form in the 4×100-metre freestyle relay, with the absence of Ashley Callus and Eamon Sullivan, Australia was never in medal territory.

In 2010, amidst sickness, Targett finished 5th in 50-metre butterfly and 14th in the 100-metre freestyle at the Telstra Australian Swimming Trials and failed to qualify for a second Commonwealth Games.

In a surprise decision by the Australian coaching staff, Targett was selected to swim the butterfly leg of the 4×100-metre medley relay in the heats.