Kneale departs at the end of July after 26 years at the company. He first joined Boots in 1976 and, apart from three years as Waterstone's as managing director, has remained there ever since. He is leaving by mutual agreement.
Formerly the chief operating officer, Kneale became chief commercial officer in October 2003.
The role of chief commercial officer has been split. It will be shared between Alex Gourlay and Ian Filby, who take up their roles in July.
Acting retail director Alex Gourlay has been appointed to the new role of healthcare and store development director, while lifestyle commercial director Ian Filby has been appointed to the new role of beauty & lifestyle director.
Boots chief executive Richard Baker said: 'David has made a very significant contribution to Boots and I would like to thank him for his commitment over the past few years and to wish him every success in the future. I am confident that the new structure will enable us to focus more effectively on our core priorities for growth. I congratulate Alex and Ian on their new roles and look forward to working with them on building a better Boots'.