Gamble will start at five-eighth in place of Ezra Mam, who struggled in last week's 53-6 loss to Parramatta, as the Broncos fight to secure the finals berth that looked a certainty only five weeks ago.
Having lost four of their last five games, the Broncos must defeat the Dragons in Sydney on Saturday evening to return to the top eight, but also need Canberra to lose to the last-placed Wests Tigers to play finals football.
Gamble's eight NRL appearances this season have all resulted in Brisbane wins, but the 26-year-old has been playing reserve grade since round 19 and has not started as Reynolds' halves partner since round 10.
Broncos coach Kevin Walters has also recalled young winger Selwyn Cobbo, who was controversially rested last week, and is welcoming back forward pack linchpin Patrick Carrigan from a four-match suspension.
With the minor premiership secured two weeks ago, Penrith have rested 12 players for their last regular-season game against North Queensland.
Hooker Mitch Kenny will captain the side, which features debutants Tom Jenkins, Jack Cole and Liam Henry and only one member of last year's premiership-winning team - Scott Sorensen.
The Cowboys have named Hamiso Tabuai-Fidow to start at five-eighth for the first time in his career but he could be replaced by Tom Dearden, who has been recovering from a testicular injury and will be a game-day decision.
Their finals spot sealed, South Sydney have opted against resting players for the first NRL game at the new Allianz Stadium, against the Sydney Roosters on Friday.
Latrell Mitchell was given Tuesday off training but will play, with Damien Cook (COVID-19) and Campbell Graham (concussion) the only notable omissions for Souths.
Cook tested positive on Saturday but is a chance to line up with the NSW Government approving cuts to the seven-day COVID-19 isolation period this week.
The hooker will not be rushed back, though, with Siliva Havili taking his place in the side and Jaxson Paulo subbing in for Graham.
The Roosters are also locked in to play finals and have named Paul Momirovski as their replacement for winger Daniel Tupou (groin injury).
Sio Siua Taukeiaho shifts to lock to cover for Victor Radley (concussion) and with Lindsay Collins suspended, Fletcher Baker and Terrell May join the bench.
Collins' hip-drop tackle left Tom Eisenhuth with a season-ending ankle injury last week, forcing Melbourne to call Chris Lewis into the side to face Parramatta on Thursday.
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