Buxton suffered a dislocated thumb during Gloucester's Guinness Premiership final defeat to Leicester on Sunday and would not be fit in time for the first Test.
Skirving, 23, has been promoted from the England Saxons Churchill Cup squad.
England head coach Brian Ashton said: "Pete's right thumb was repositioned last night and although the prognosis is good, unfortunately he won't be able to take a full part in preparation for the first Test.
"It is unfortunate for Pete but we have decided to call up Ben Skirving from the England Saxons to travel in his place."
England fly to South Africa tomorrow and face the Springboks at altitude in Bloemfontein on May 26 and Pretoria on June 2.