The comments add to pressure on British Prime Minister Theresa May to rethink her plan for leaving the EU after Brexit talks reached a stand-off at the weekend over arrangements for the UK border with Ireland.
"If a transition deal does not make clear what will happen in the future, we will maintain our decision not to invest," Leif Johansson told France's Le Monde newspaper.
"A Brexit agreement will need to ensure that Britain does not become an isolated island in the middle of the Atlantic Ocean," he added.
A spokesman for AstraZeneca said Johansson was referring to a freeze on investments in manufacturing announced in 2017.
"There has been no change to our investment plans in the UK," the spokesman said.
AstraZenca has already spent 40 million pounds ($53 million) stockpiling medicines in Britain and continental Europe to prevent supply disruptions if the two sides fail to reach a withdrawal agreement.
Some pharmaceutical companies including AstraZeneca have warned of medicine shortages in the event of a 'no deal' Brexit.
More than 2,600 drugs have some part of their manufacturing carried out in Britain. Britain exports some 45 million medical packs to EU countries each month, industry figures show, while 37 million flow to Britain from the EU.
France's largest drugmaker Sanofi said in August it would increase medicine stockpiles in Britain, echoing moves made by GlaxoSmithKline, Roche and Novartis.
"In business, uncertainty often forces you to make decisions. But what is frustrating is to have to do so when the existing system works very well," Johansson said. "This is costing us money and brings us no benefit."
($1 = 0.7602 pounds)
(Reporting by Inti Landauro; Editing by Richard Lough and Mark Potter)