Grayson has not started since the Premiership Rugby Cup defeat at Harlequins in November, and has only featured once since then, coming off the bench at Worcester on January 29.
But he is back in the first 15 this weekend, with George Furbank moving to full-back.
Tom Collins also gets a rare start, replacing Ollie Sleightholme on the wing, while Rory Hutchinson is not involved.
Hutchinson is on the 'not considered for selection' list alongside the likes of Teimana Harrison and Juarno Augustus, who are ruled out this weekend.
It means Saints have a much-changed pack, with Sam Matavesi moving from hooker to seven, Karl Wilkins switching to No.8 and Alex Coles coming in at six.
Api Ratuniyarawa is in at lock while Mike Haywood comes in at hooker, but young props Manny Iyogun and Ehren Painter keep their place after impressing in the 22-21 defeat to Sale Sharks last weekend.
Alex Moon and Tom James return from injury and are named among the replacements.
Saints: Furbank; Skosan, Proctor, Dingwall (c), Collins; Grayson, Mitchell; Iyogun, Haywood, Painter; Ribbans, Ratuniyarawa; Coles, Matavesi, Wilkins.
Replacements: Fish, Waller, Hill, Moon, Nansen, Tonks, James, Francis.
Exeter Chiefs: Hodge; Woodburn, Whitten, Hendrickson, O'Flaherty; J Simmonds, S Maunder; Hepburn, Innard, Schicklerling; Kirsten, Jenkins; Ewers, Capstick, Grondona.
Replacements: Yeandle, Kenny, Street, Pearson, Norey, J Maunder H Skinner, Cordero.