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).
Gilbert has released a new line of rugby cleats. The Gilbert Virtuo 8S is part of the exciting new product. Check it out.
The Barbarians are one of the top invitational rugby sides with a long history and classic rugby jersey.
The Nike Tiempo is a solid rugby cleat and one of few styles still made from full-grain natural leather.
The Lions get ready for their matches with this green training jersey. It's what the players wear. Get in the Gear!
A cool looking all black rugby cleat with the high performance adidas is known for. Get in the Gear!
Wear the crest of the British and Irish Lions on your t-shirt. A great look for the summer.
The Lions are ready to get their Australia tour underway. They arrive in Perth on Monday.
The New Zealand All Blacks training jersey for 2013/14. Get in the Gear!
The USA Rugby Pro Alternate rugby jersey is perfect for any fan of the Eagles. Get yours to wear during the summer Test matches.
The NEW All Blacks 2013/14 jersey has arrived at World Rugby Shop. Dare to wear the colors of the All Blacks.