Murray, who signed for Warriors last month, last featured for Scotland on the successful summer tour to Australia, Fiji and Samoa.
The 32-year-old impressed sufficiently to return at the expense of Cross, who scored his first Test try against the All Blacks at the weekend.
Scotland head coach Andy Robinson said: "I was pleased with Euan's contribution both at scrummage and in open play during the summer tour.
"We know we're in for a bruising battle against South Africa this weekend and we will be primed for that physical confrontation.
"But we also have to be smart in how we approach this game and do our utmost to ensure we get on the front foot and get the result that will move us into the top eight in the IRB world rankings ahead of next month's 2015 Rugby World Cup draw."
Murray was named man of the match when the two nations clashed at Murrayfield in 2008 and the prop will be hoping for a similar performance this time around.
Murray signed for Warriors after spending the first part of the season on loan to French club Agen.
He will join up with his new teammates in time for the Aviva Premiership clash with Harlequins at the end of the month.
Scotland team to play South Africa at Murrayfield on Saturday:
Backs: S Hogg (Glasgow Warriors) S Lamont (Glasgow Warriors), N De Luca (Edinburgh), M Scott (Edinburgh), T Visser (Edinburgh), G Laidlaw (Edinburgh), M Blair (Brive)
Forwards: R Grant (Glasgow Warriors), R Ford (Edinburgh), E Murray (Worcester Warriors), R Gray (Sale Sharks), J Hamilton (Gloucester), A Strokosch (Perpignan), K Brown (captain, Saracens), D Denton (Edinburgh)
Substitutes D Hall (Glasgow Warriors), K Traynor (Bristol), G Cross (Edinburgh), A Kellock (Glasgow Warriors), J Barclay (Glasgow Warriors), H Pyrgos (Glasgow Warriors), R Jackson (Glasgow Warriors), P Murchie (Glasgow Warriors)