Tuipulotu replaces his Glasgow Warriors team-mate Sam Johnson at inside centre, with Johnson released to play for his club against Munster on Friday night.
The starting front row is the trio that finished the match against England last weekend. It means Pierre Schoeman, Stuart McInally and WP Nel replace Rory Sutherland, George Turner and Zander Fagerson who are all on the bench.
The other change is at blindside flanker where Sam Skinner of Exeter Chiefs comes in for the injured Jamie Ritchie.
Rory Darge is on the bench as back-row cover and is in line to win his first Scotland cap.
Cam Redpath is also added to the bench after recovering from a serious knee injury. The Bath centre has not played for Scotland since his impressive debut in last season’s Calcutta Cup win.
Scotland, who have not won in Cardiff for 20 years, are looking to build on their opening day victory over England.
Saturday’s match kicks off at 2.15pm at the Principality Stadium and is live on BBC One.