Smith is preferred for the first of four matches ahead of Owen Farrell and George Ford, both of whom started the Premiership final on May 27.
Steve Borthwick names his World Cup squad on Monday and, with Smith thought to be behind Farrell and Ford in the pecking order, he has the platform at the Principality Stadium to convince his head coach that a third fly-half should be taken to France.
Danny Care joins the 24-year-old at half-back and the side is littered with fringe contenders for the final 33-man group - with no players from Premiership finalists Saracens and Sale present in the starting XV.
Ellis Genge captains the team but, apart from Care, it is an inexperienced line-up, with fast-rising Northampton flanker Tom Pearson making his debut at openside.
England play Wales at Twickenham the following weekend before fixtures against Ireland and Fiji later in August.
Borthwick's team launch their World Cup campaign against Argentina in Marseille on September 9.
