Wilkinson has been sidelined since Newcastle's Premiership defeat to London Irish earlier this month, when he limped off six minutes from time nursing a hamstring problem.
He then missed England's RBS 6 Nations appointments with France and Wales, and his Newcastle colleague Toby Flood took over Test fly-half duties.
The 55 times-capped World Cup winner lines up in a Newcastle side also boosted by his returning England colleagues Flood, Mathew Tait and Jamie Noon.
Flood will wear the number 11 shirt, with Tait and Noon forging Falcons' midfield partnership.
