The Anglo-Swedish drugs company owes the Government over so-called transfer pricing – the price at which a group sells goods or services from one section to another.
Astra will pay £350m next month and a second installment of £155m in March next year.
The tax claims go as far back as 1996.
HMRC is cracking down on internal transfers of expenses or profits.
The compamy said in a statement: “AstraZeneca has provided in its accounts for the outcome of this issue, at the heart of which are complex transfer price considerations that have taken many years to resolve.”