Slade did not feature at all during England's woeful Six Nations, where they lost four out of their five games.
But the 33-year-old centre had a strong finish to the domestic season, leading Exeter to the Prem final.
Slade's return means Northampton's Tommy Freeman is deployed in his more familiar wing role following a year-long effort to convert him into an outside centre.
Guy Pepper replaces Tom Curry at openside flanker in the other change to the starting XV beaten 45-21 by world champions South Africa in their Nations Championship opener in Johannesburg last week.
Meanwhile, the uncapped trio of South Africa-born Benhard Janse van Rensburg, Noah Caluori and George Kloska could all make their Test debuts off the bench.
England (15-1):
Marcus Smith; Tommy Freeman, Henry Slade, Seb Atkinson, Immanuel Feyi-Waboso; Fin Smith, Jack van Poortvliet; Ben Earl, Guy Pepper, Ollie Chessum; George Martin, Alex Coles; Joe Heyes, Jamie George (capt), Ellis Genge
Replacements: Luke Cowan-Dickie, Asher Opoku-Fordjour, George Kloska, Tom Curry, Henry Pollock, Alex Mitchell, Benhard Janse van Rensburg, Noah Caluori
Coach: Steve Borthwick (ENG)