Ryan Pringle and George Harding will leave the club when their contracts expire at the end of the 2019 season.
All-rounder Pringle made 40 First-Class and 40 List A appearances for the Ds and was part of the side that reached the 2016 T20 Final against Northants at Edgbaston.
The 27-year-old scored an impressive 125 against Derbyshire in the 2016 One Day Cup and grabbed over 100 wickets in all formats.
Left-arm spinner Harding made just three First Class appearances for Durham after making his debut against Gloucestershire in 2017.
The Dorset born 22-year-old recorded 12 wickets in 11 games across all formats.
Durham Cricket’s Director of Cricket, Marcus North, said: “We would like to wish both Ryan and George the very best for their future careers and thank them for their commitment to Durham Cricket.”