Otago have a proud record against the Lions, winning four of their seven matches against the tourists.
"I'm very proud to be having my first game for Otago, especially against the Lions," said the fly-half.
"It is going to be a huge occasion."
It will also be a huge occasion for Newby, who will captain Otago in the absence of veteran hooker Anton Oliver, who is battling hard to recover from a calf injury in time to take his place in the All Blacks squad.
Also missing from the Otago line-up are prop Carl Hayman and lock James Ryan who are preparing for the All Blacks' three Tests.
But with 13 players in the Otago starting XV boasting Super 12 experience and four of those - Evans, Newby, Josh Blackie and prop Carl Hoeft, who has 30 All Blacks caps to his name - in the Junior All Blacks, the Lions will not have everything their own way.
Otago team to face the Lions in Carisbrook on Saturday: Glen Horton; Hayden Pedersen, Neil Brew, Seilala Mapusua, Matt Saunders; Nick Evans, Danny Lee; Carl Hoeft, Jason Macdonald, Craig Dunlea, Filipo Levi, Tom Donnelly, Craig Newby (c), Josh Blackie, Grant Webb.
Replacements: Jed Vercoe, Jeremy Aldworth, Andrew McClintock, Alando Soakai, Chris Smylie, Ryan Bambry, Jason Shoemark.