The game marks the opening of the Edinburgh Rugby Stadium and sees fans return to watch the club in full numbers for the first time since February 2020.
Scotland hooker Dave Cherry has been named as captain of an enlarged 32-man squad which is likely to see plenty of rotation in the pre-season friendly.
Immelman, who joined Edinburgh from French Top 14 side Montpellier, is picked at full-back, with wingers Jack Blain and Damien Hoyland completing the back-three.
Darcy Graham has been ruled out through injury.
Scrum-half Vellacott, who was signed from Wasps, is paired with Scotland international Jaco van der Walt at half-back.
South African de Bruin packs downs with fellow South African prop Boan Venter either side of Cherry in the front-row.
Four other new recruits – Harry Lloyd, Adam McBurney, Pierce Phillips and Ramiro Moyano – are named among the replacements, as are FOSROC Super6 players Daniel Suddon and Patrick Anderson.
Blair said: “This Saturday we celebrate something much bigger than 80 minutes. It’s an exciting moment in Edinburgh Rugby’s history and a fresh start that our supporters, players and everyone connected to the club have been looking forward to.
“As a team, we cannot wait to run out into the ERS for the first time, and to do so in front of our supporters, who’ve waited so patiently for this day through the midst of a pandemic, will be a really special moment.”
Edinburgh (v Newcastle Falcons, ERS, Saturday, 3pm)
15. Henry Immelman; 14. Jack Blain, 13. Mark Bennett, 12. Cammy Hutchison, 11. Damien Hoyand; 10. Jaco van der Walt, 9. Ben Vellacott; 1. Boan Venter, 2. David Cherry, 3. Luan de Bruin, 4. Marshall Sykes, 5. Jamie Hodgson, 6. Magnus Bradbury, 7. Luke Crosbie, 8. Nick Haining.
Subs: Pierre Schoeman, Harry Lloyd, Adam McBurney, Patrick Harrison, Lee-Roy Atalifo, Angus Williams, Pierce Phillips, Daniel Suddon, Ben Muncaster, Connor Boyle, Charlie Shiel, Henry Pyrgos, Charlie Savala, Ramiro Moyano, Jordan Venter, James Johnstone, Patrick Anderson.