Bird pulled his hamstring while bowling in a domestic match in Brisbane last weekend and is expected to be sidelined for up to three weeks, opening the door for the uncapped Sayers.
"It's disappointing for Jackson, but it is exciting for Chadd at the same time," Australian captain Steve Smith said.
"It's kind of a like for like sort of bowler, they're pretty similar. They both stand the seam up nicely and Chadd's been rewarded for what he has done in Shield cricket over the last couple of years, which is great."
"He's a difficult one (to face)," Smith added. "Because he is so short not many balls go over the stumps, which makes him a pretty handy proposition when the ball is seaming around. I think it is a good selection."
Sayers joins fellow quicks Mitchell Starc, Josh Hazelwood, Pat Cummins and Jye Richardson for the four-Test South Africa series which kicks off on March 1.
Australia - Steve Smith (capt), David Warner, Cameron Bancroft, Pat Cummins, Peter Handscomb, Josh Hazlewood, Jon Holland, Usman Khawaja, Nathan Lyon, Mitchell Marsh, Shaun Marsh, Tim Paine, Jhye Richardson, Chadd Sayers, Mitchell Starc.
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