The explosive 20-year-old has been given a chance to press his World Cup selection claims in the first of England's three warm-up internationals.
"I'm really proud to be winning my first cap," said Tuilagi, who was voted Aviva Premiership young player of the year last season.
"There is a lot of competition for places and I just want to take this chance and do the best I can for the team.
"The boys have worked hard during the camp but now we have to perform against Wales."
Saracens lock Mouritz Botha and Gloucester wing Charlie Sharples are both primed to make their Test debuts off the bench.
Tuilagi, whose four elder brothers have played Test rugby for Samoa, will start in a new-look midfield partnership alongside Riki Flutey.
England's starting XV features a number of comebacks.
Flutey, the Wasps centre, and London Irish full-back Delon Armitage both get an England start for the first time since the 2010 Six Nations.
Saracens prop Matt Stevens earned his last England cap in November 2008, shortly after which he tested positive for cocaine and was banned for two years.
Lewis Moody missed the Six Nations title campaign with knee ligament damage but he returns to captain the team in a back row that features Tom Croft at blindside flanker and James Haskell at number eight.
Matt Banahan and Mark Cueto start on the wings while Jonny Wilkinson and Danny Care fill the half-back slots in a strong but experimental England line-up.
England team v Wales: D Armitage (London Irish); M Banahan (Bath Rugby), M Tuilagi (Leicester Tigers), R Flutey (London Wasps), M Cueto (Sale Sharks); J Wilkinson (Toulon), D Care (Harlequins); A Corbisiero (London Irish), D Hartley (Northampton Saints), M Stevens (Saracens), S Shaw (Unattached), T Palmer (Stade Francais), T Croft (Leicester Tigers), L Moody (Bath Rugby, capt), J Haskell (Ricoh Black Rams).
Replacements: L Mears (Bath Rugby), D Wilson (Bath Rugby), M Botha (Saracens), T Wood (Northampton Saints), R Wigglesworth (Saracens), C Hodgson (Saracens), C Sharples (Gloucester Rugby).
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