Simons left Christian Dior last October after three years heading up the iconic French brand.
In a statement on Facebook, Calvin Klein said: "Mr Simons will lead the creative strategy of the Calvin Klein brand globally...Mr Simons' first collections will debut for the Fall 2017 season."
The company said the appointment is part of its strategy to "unify all Calvin Klein brands under one creative vision" and "strengthen the brand's premium positioning" as it aims to hit $10bn in global retail sales.
"The arrival of Raf Simons as chief creative officer signifies a momentous new chapter for Calvin Klein," said Steve Shiffman, Calvin Klein's chief executive.
“Not since Klein himself was at the company has it been led by one creative visionary, and I am confident that this decision will drive the Calvin Klein brand and have a significant impact on its future.
"Raf’s exceptional contributions have shaped and modernised fashion as we see it today and, under his direction, Calvin Klein will further solidify its position as a leading global lifestyle brand.”