Boots' UK boss Simon Roberts is set to quit the company in July to "pursue new opportunities".
Roberts, who is also executive vice-president of Boots' American owner Walgreens Boots Alliance, said that the pharmacy chain now needs a "new leader to take the business forward".
Roberts joined Boots from Marks & Spencer in 2003 and was promoted to president as part of Boots' merger with Walgreens.
Walgreens Boots Alliance announced that Elizabeth Fagan, currently senior vice-president and managing director of the company's international retail division, will become senior vice-president and managing director of Boots.
The group also said its executive vice president Alex Gourlay and Ornella Barra, head of global wholesale and international retail, would become co-chief operating officers.
Roberts said: "Over the past three years we have achieved good progress in modernising our business to be better prepared for the opportunities and challenges of today's world and the strategy and plans to build an even better Boots are well on track.
"I've therefore come to realise that now is the right time for me to step away and consider new opportunities for the future, and for a new leader to take the business forward in the next phase."
Stefano Pessina, executive vice-chairman and chief executive officer of Walgreens Boots Alliance, said: "I would like to warmly thank Simon for his outstanding contribution and for the key role he played at Boots during the past 13 years of his career.
"We wish him the very best for the future."