The fit-again Brian Murphy replaces Conor Finn to form the centre partnership with Tadhg Leader.
Steve Macauley replaces Matt Healy on the left wing with Shane Layden reverting to the right wing from full-back. Matthew Jarvis will start at full-back.
Up front, there is an entirely new front row trio. Kevin O'Byrne has been promoted from the bench to starting hooker and is joined by year 1 Academy member Finlay Bealham at loosehead prop and New Zealander Rodney Ah You on the tighthead side.
Both Thomas Anderson, who captains the province, and Eoin McKeon return to action this weekend. They join Eoghan Grace in an athletic back row combination.
Kick-off at Dubarry Park, the home of Buccaneers RFC, is at 7.45pm. Connacht Rugby Season Ticket holders are granted access to all of the Eagles home British & Irish Cup games.
CONNACHT EAGLES (v Newcastle Falcons): Matthew Jarvis; Shane Layden, Brian Murphy, Tadhg Leader, Steve Macauley; Jack Carty, Marcus Walsh; Finlay Bealham, Kevin O'Byrne, Rodney Ah You, Michael Kearney, Daniel Qualter, Thomas Anderson (capt), Eoghan Grace, Eoin McKeon.
Replacements: Peter Reilly, JP Cooney, Jonathan Gardiner, David Heffernan, Mark Dolan, Conor Finn, Darragh Leader.