The 20-year-old Samoan will partner Kiwi Riki Flutey in the heart of England’s midfield while veteran Jonny Wilkinson will pull the strings from fly half.
“I’m really proud to be winning my first cap,” said Tuilagi, who was voted 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.”
Tuilagi will be the fifth member of his family to play international rugby, with his four brothers having played for Samoa.
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.
England team to play Wales in the Investec international at Twickenham on Saturday, Aug 6 (2.30pm kick-off):
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).