Hamilton, who gained his first two senior caps with outings during the autumn internationals, will wear the No.5 shirt and lines up alongside Alastair Kellock of Glasgow Warriors in the Scots' second row, with the experience Scott Murray on the bench.
The 6ft 8in Hamilton came through the full 80 minutes of Tigers' 39-5 victory over Newcastle Falcons on Saturday and then joined up with his national squad colleagues.
He will come face to face with clubmate Louis Deacon, who has been named in the England second row, as well as Martin Corry, George Chuter and Harry Ellis.
Scotland head coach Frank Hadden said: "Alastair Kellock has been at the heart of Glasgow's progress this season. As their captain he has grown in stature and we think he forms a formidable second-row combination alongside James Hamilton."
Scotland team (vs England, Saturday, kick-off 4pm)
15 Hugo Southwell (Edinburgh Rugby)
14 Sean Lamont (Northampton Saints)
13 Marcus Di Rollo (Edinburgh Rugby)
12 Andrew Henderson (Glasgow Warriors)
11 Chris Paterson (Edinburgh Rugby, captain)
10 Dan Parks (Glasgow Warriors)
9 Chris Cusiter (Border Reivers)
1 Gavin Kerr (Border Reivers)
2 Dougie Hall (Edinburgh Rugby)
3 Euan Murray (Glasgow Warriors)
4 Alastair Kellock (Glasgow Warriors)
5 James Hamilton (Leicester Tigers)
6 Simon Taylor (Edinburgh Rugby)
8 David Callam (Edinburgh Rugby)
7 Kelly Brown (Border Reivers)
Replacements
16 Ross Ford (Border Reivers)
17 Allan Jacobsen (Edinburgh Rugby)
18 Scott Murray (Edinburgh Rugby)
19 Allister Hogg (Edinburgh Rugby)
20 Rory Lawson (Gloucester)
21 Rob Dewey (Edinburgh Rugby)
22 Rory Lamont (Glasgow Warriors)
