The Wasps full-back missed England's Six Nations victory over Italy but is back to full fitness and reclaims the number 15 jersey from club colleague Tom Voyce, who drops back to the bench.
The only other change to the starting XV made by head coach Andy Robinson for the trip to Murrayfield, where England face a resurgent Scotland side on Saturday, is to replace the injured Matt Stevens with Leicester tight-head prop Julian White.
Stevens impressed against both Wales and Italy but strained his shoulder in Bath's defeat to London Irish. White starts his first England game in more than a year.
Robinson has made three changes to the bench. White's promotion opens a spot among the replacements for Perpignan prop Perry Freshwater, while uncapped Leicester hooker George Chuter replaces Bath's Lee Mears.
With Lewsey back and Voyce on the bench, Gloucester's James Simpson-Daniel - who scored England's final try against Italy - is forced out of the equation.
Voyce, who replaced Lewsey in the first half against Wales, was passed fit for selection despite losing three teeth in Wasps' 9-9 draw with Bristol.
White started his last England game in the 11-9 defeat to Wales which opened last season's Six Nations championship.
He started all three British & Irish Lions Tests in New Zealand but was overlooked for England's autumn internationals because Robinson was looking to inject more mobility and footballing skill into his forward pack.
England head north as the only unbeaten side in the championship after the 47-13 drubbing of Wales and the hard-fought 31-16 victory over Italy - their first away win since 2004.
But Robinson will be expecting a far more rigorous test in the Scottish capital than perhaps he might have expected two months ago.
Scotland, under new coach Frank Hadden, opened their campaign with a dramatic victory over pre-tournament favourites France and battled hard against Wales last week after being reduced to 14 men.
England team to play Scotland in the Six Nations Championship on Saturday:
J Lewsey (Wasps); M Cueto (Sale Sharks), J Noon (Newcastle), M Tindall (Gloucester), B Cohen (Northampton); C Hodgson (Sale Sharks), H Ellis (Leicester); A Sheridan (Sale Sharks), S Thompson (Northampton), J White (Leicester), S Borthwick (Bath), D Grewcock (Bath), J Worsley (Wasps), L Moody (Leicester), M Corry (capt, Leicester).
Replacements: G Chuter (Leicester), P Freshwater (Perpignan), S Shaw (Wasps), L Dallaglio (Wasps), M Dawson (Wasps), A Goode (Leicester), T Voyce (Wasps