Myler replaces Harry Mallinder, who has started all six games at fly-half this season.
Piers Francis, who made his Saints debut in the 29-24 defeat at Gloucester last Saturday, keeps his place at inside centre, with Luther Burrell staying at 13.
Australian ace Rob Horne misses out with a calf injury.
But Nic Groom does return from an ankle knock to take his place on the bench, with Cobus Reinach retaining the No.9 shirt.
Ben Foden starts for the first time since the 55-24 Aviva Premiership opening-day defeat to Saracens at Twickenham as he replaces Tom Collins on the wing.
In the pack, Courtney Lawes returns to first 15 having been given a little breather on the bench last weekend. He replaces Sam Dickinson, with Teimana Harrison moving to No.8.
Tom Wood makes a welcome return from a shoulder injury as he is named among the replacements after scoring twice against Cambridge University on Monday night.
Meanwhile, Calum Clark will make his first appearance at Franklin's Gardens since moving to Saracens during the summer as he starts at seven for the European champions.
Owen Farrell is fit enough to start at fly-half after missing the win against Wasps due to a calf strain.
Saints: Tuala; North, Burrell, Francis, Foden; Myler, Reinach; Waller, Hartley (c), Brookes; Paterson, Ribbans; Lawes, Gibson, Harrison.
Replacements: Haywood, van Wyk, Ford-Robinson, Ratuniyarawa, Wood, Groom, Mallinder, Collins.
Saracens: Goode; Williams, Bosch, Barritt (c), Wyles; Farrell, Wigglesworth; M Vunipola, George, Koch; Isiekwe, Kruis; Itoje, Clark, Wray.
Replacements: Brits, Barrington, Figallo, Day, Burger, Spencer, Lozowski, Taylor.