Imperial Brands Plc Chief executive officer Alison Cooper will step down once a replacement is found, the maker of Winston and Gauloises cigarettes announced on Thursday.
The departure of Cooper, who has led the company for nine years, comes days after it issued a full-year profit warning blaming the US regulatory crackdown on vaping.
Cooper is one of just five female CEOs among Britain's top 100 listed companies.
In July the company announced that it would drop its 10% dividend growth target from next year to focus on developing its e-cigarette portfolio as traditional smoking wanes.
This added to investor woes as stocks such as Imperial have historically been sought after for their high earnings and dividend payments.
While the search for a successor continues, Cooper will focus on driving the performance of the business, including the asset divestment programme, from which the company expects to realise proceeds of up to £2 billion ($2.46 billion) by May 2020, the company said in a statement.
Cooper's departure is the second high profile exit for the company this year. It announced in February that Chairman Mark Williamson would step down once a successor was found citing new British guidelines on the length of board chair tenures.