Chessum will now partner England captain Maro Itoje in the second row in a direct swap for George Martin, who has been managing a knee problem and drops to the bench for the Calcutta Cup clash in a team announced by coach Steve Borthwick on Tuesday.
It will be Chessum's first start for England since last year's Six Nations, having been ruled out of the subsequent tour of Japan and New Zealand and the November internationals by shoulder and knee injuries.
But the 24-year-impressed off the bench in England's opening defeat by champions Ireland and their stunning 26-25 win at home to France last time out.
"We are looking forward to what will be another challenging and exciting match against Scotland," said Borthwick.
The former England captain added: "The Calcutta Cup is a special fixture and we are determined to perform to our very best in front of our supporters at Allianz Stadium (Twickenham)."
Scotland are on a four-game winning streak against England, although they were well-beaten 32-18 by Ireland at Murrayfield in the second round.
Gregor Townsend, the Scotland coach, is due to name his side on Thursday.
England (15-1)
Marcus Smith; Tommy Freeman, Ollie Lawrence, Henry Slade, Ollie Sleightholme; Fin Smith, Alex Mitchell; Tom Willis, Ben Earl, Tom Curry; Ollie Chessum, Maro Itoje (capt); Will Stuart, Luke Cowan-Dickie, Ellis Genge
Replacements: Jamie George, Fin Baxter, Joe Heyes, George Martin, Chandler Cunningham-South, Ben Curry, Harry Randall, Elliot Daly
Coach: Steve Borthwick (ENG)