2005 Lions Test scrum-half Dwayne Peel returns after injury but fellow Lion Michael Owen misses out despite injuries to fellow back-row players Jonathan Thomas and Gareth Delve.
Luke Chateris and Robin Sowden-Taylor are also given another opportunity to impress at international level but Blues centre Jamie Robinson will not be involved against South Africa, Canada, New Zealand and Australia.
"It's particularly pleasing to be able to select two players in Daniel Biggar and Leigh Halfpenny who stood out for Wales in the Junior World Championships in the summer and Martin Roberts has shown enough for his region to be deserving of his chance," said Gatland.
"Andy Powell has been playing well for some time and his performance at the weekend was there to convince us of his ability if we had needed any convincing.
"Eifion Roberts is another who has been on the radar and he now gets his chance to sample life at international level.
"Robin Sowden-Taylor is just coming back from injury, but we are looking for him to come through and provide cover in the back row during the course of the four-match series and there are one or two others who we have shown some loyalty towards.
"This squad is larger than I would normally select, and we may reduce it after we get the first two games under our belts. But the current size reflects the fact that we could be asking some players to turn out three times in the space of 13 days.
"The Ospreys players, for example, are currently due to play for their region on the Sunday before the South Africa game, and with the Canada match coming only six days later, we will need to use our squad correctly."
Backs: Gareth Cooper, Dwayne Peel, Martin Roberts, Stephen Jones, James Hook, Daniel Biggar, Jamie Roberts, Andrew Bishop, Tom Shanklin, Gavin Henson, Shane Williams, Mark Jones, Leigh Halfpenny, Lee Byrne, Morgan Stoddart
Forwards: Gethin Jenkins, Duncan Jones, Huw Bennett, Matthew Rees, Richard Hibbard, Adam Jones, Eifion Roberts, Rhys Thomas, Alun-Wyn Jones, Ian Gough, Ian Evans, Luke Charteris, Dafydd Jones, Andy Powell, Martyn Williams, Robin Sowden-Taylor, Ryan Jones (captain)