Ali Price, Rory Sutherland and Elliot Daly are the players to make way as the Lions look to seal a series victory over South Africa.
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.