Duffield, 26, has committed to Fremantle until the end of the 2014 season, while Mayne, 22, has signed a two-year extension, keeping him at the club until the end of 2013.
Both players are members of Fremantle's leadership group and were previously out of contract at the end of the 2011 season, making them potential targets of new franchise Greater Western Sydney.
Fremantle general manager of player management Brad Lloyd said it was exciting to have the pair re-sign.
"We are delighted to have Paul and Chris commit to the club because they are both young leaders and very important players,” Lloyd said.
The latest re-signings continue Fremantle's enviable run of warding off Gold Coast and GWS, with captain Matthew Pavlich and key midfielder David Mundy last year signing four-year deals to remain at Fremantle.
Duffield played all 24 games for Fremantle last season - including two finals - leading the AFL for rebound 50s and emerging as one of the competition's top-line half-backs.
Mayne, who was recruited with pick No.40 in the 2007 NAB AFL Draft, played 17 games in an accomplished debut 2008 season, but he has since been plagued by injuries.
The hard-tackling forward has enjoyed his first full pre-season since joining Fremantle and received a massive vote of confidence from his teammates when he was voted into the club's leadership group last December after just 36 AFL games.
Giants coach Kevin Sheedy this week singled out Fremantle as a club GWS would target in an effort to boost its list ahead of its inaugural season.
2008 NAB AFL Rising Star Rhys Palmer is out of contract at the end of 2011, as are utility players Kepler Bradley and Michael Johnson.
Paul Duffield is a $363,900 defender in the Toyota AFL Dream Team competition
