Murray takes the scrum-half duties from Ali Price, who drops to the bench in a straight swap of roles from the series opener at Cape Town Stadium that saw the Lions emerge 22-17 winners.
Vunipola is rewarded for his impact off the bench in the first Test, which included a solid scrummaging performance, by getting the nod ahead of Rory Sutherland at loosehead prop.
Sutherland struggled at the set-piece and with Wyn Jones suffering from a shoulder problem, the Scotland front row is needed among the replacements.
The final adjustment to the XV that have placed the Lions on the brink of a first series victory over South Africa since 1997 is Harris’ promotion from outside the 23 to replace Elliot Daly in the centres.
Lions XV for second Test
15-Stuart Hogg, 14-Anthony Watson, 13-Chris Harris, 12-Robbie Henshaw, 11-Duhan van der Merwe, 10-Dan Biggar, 9-Conor Murray, 8-Jack Conan, 7-Tom Curry, 6-Courtney Lawes, 5-Alun Wyn Jones (captain), 4-Maro Itoje, 3-Tadhg Furlong, 2-Luke Cowan-Dickie, 1-Mako Vunipola
Replacements: 16-Ken Owens, 17-Rory Sutherland, 18-Kyle Sinckler, 19-Tadhg Beirne, 20-Taulupe Faletau, 21-Ali Price, 22-Owen Farrell, 23-Elliot Daly.