Grayson comes into the team in place of Dan Biggar, who has progressed well while going through his concussion protocols but is given an extra week to rest and recover.
Piers Francis is ruled out with a quadriceps injury, meaning Rory Hutchinson and Matt Proctor form the centre partnership.
Ollie Sleightholme returns from a back injury to take his place on the wing, with another of the season's young stars, Tommy Freeman, on the other side of the field.
There are no changes to the pack that played in the 31-7 defeat at home to Gloucester last weekend.
But Mike Haywood is fit enough to return from a hand injury to take his place on the bench.
Francis (quadricep), Owen Franks (foot), Danny Hobbs-Awoyemi (Achilles), Nick Isiekwe (pectoral), Courtney Lawes (pectoral) and Alex Mitchell (ankle) make up the injured list.
Saints will be up against an extremely familiar face on Monday as Luther Burrell, who helped the black, green and gold to a Premiership and Challenge Cup double in 2014, starts at inside centre for the home side.
Up to 1,750 fans will be in attendance at Kingston Park following the easing of government restrictions.
Newcastle Falcons: Penny; Radwan, Orlando, Burrell, Wacokecoke; Connon, Shreuder; Brocklebank, McGuigan, Davison; Peterson, Robinson; Welsh, Wilson (c), Chick.
Replacements: Blamire, Cooper, Tampin, van der Walt, Fearns, Stuart, Hodgson, Obonna.
Saints: Furbank; Sleightholme, Proctor, Hutchinson, Freeman; Grayson, James; Waller (cc), Matavesi, Hill; Ribbans, Ratuniyarawa; Wood, Ludlam (cc), Harrison.
Replacements: Haywood, Auterac, Painter, Coles, Adendorff, Taylor, Dingwall, Collins.