The 24-year-old had not played for his country since a groin injury sidelined him for 15 months.
Having made a comeback in January to his club side Leicester, he then suffered a hamstring injury that again kept him off the pitch.
He takes the place of Saracens full-back Andy Goode, while exciting Wasps centre Elliot Daly is retained. Tuilagi is like to start on the replacements bench.
England's Australian head coach Eddie Jones named a 24-man squad and will announce his starting XV on Thursday.
Luke Cowan-Dickie is the 24th player retained by Jones and is acting as injury cover for hooker Jamie George.
Prop Kieran Brookes, who makes his first appearance of the Six Nations in England's matchday 23, takes the place of his Northampton team-mate Paul Hill.
Tuilagi won the last of his 26 caps on the 2014 summer tour to New Zealand before a serious groin problem struck.
Having made his injury comeback this season, he then went down with a hamstring problem and has played just six matches for Leicester in the current campaign, although he scored a try against Exeter on Sunday.
Leicester director of rugby Richard Cockerill insists the British and Irish Lions centre is “five or six games away from being fully fit to play 80 minutes of Test rugby” and also has misgivings over his suitability for a role as a replacement given the length of time he has been out.
“Even if you put him on the bench to be an impact player for the last half an hour, what happens if you have to put him on after five minutes?” Cockerill said.
Jones, however, has already stated that Tuilagi is capable of playing 20 minutes and intends unleashing him in the final quarter against Wales as England seek to take another step towards a first Grand Slam since 2003.
The inclusion of Daly, who Jones says covers both centre positions and full-back, means Tuilagi would not be forced into action if there was an early loss to the first-choice midfield pairing of Owen Farrell and Jonathan Joseph.
England have sorely missed their midfield wrecking ball and most feared three-quarter, who feared his career might have been over amid three aborted comebacks during a torrid recovery from his groin issue.
Jones views Tuilagi exclusively as an inside centre and believes he can become England's version of New Zealand great Ma'a Nonu.
Forwards (14): Kieran Brookes (Northampton Saints), Dan Cole (Leicester Tigers), Luke Cowan-Dickie (Exeter Chiefs), Jack Clifford (Harlequins), Jamie George (Saracens), Dylan Hartley (Northampton Saints, capt), James Haskell (Wasps), Maro Itoje (Saracens), George Kruis (Saracens), Joe Launchbury (Wasps), Joe Marler (Harlequins), Chris Robshaw (Harlequins), Billy Vunipola (Saracens), Mako Vunipola (Saracens).
Backs (10): Mike Brown (Harlequins), Danny Care (Harlequins), Elliot Daly (Wasps), Owen Farrell (Saracens), George Ford (Bath Rugby), Jonathan Joseph (Bath Rugby), Jack Nowell (Exeter Chiefs), Manu Tuilagi (Leicester Tigers), Anthony Watson (Bath Rugby), Ben Youngs (Leicester Tigers). – AFP
Original source: Tuilagi back in England squad