Goulard, who was previously a member of the European Parliament, said she could not remain in the government while there was a possibility that she could be investigated over alleged misuse of expenses at that parliament.
Her resignation comes as Macron carries out a minor reshuffle of his government following parliamentary elections on Sunday which handed him and his allies MoDem a commanding majority.
But she said the possibility of an investigation made it difficult for her to stay in the post given Macron’s agenda to clean up politics.
“The president is committed to restoring confidence in public office, reforming France and relaunching Europe,” she said in a statement.
“This reform agenda must take precedence over any personal considerations.
“That is why I have asked the president, with the agreement of the prime minister, to leave the government.”
Earlier this month, Paris prosecutors opened a preliminary investigation into claims in the Canard Enchaine newspaper that MoDem was using European parliamentary funds to pay staff based in France.
MoDem’s leader Francois Bayrou was a key backer of Macron’s one-year-old Republic on the Move (REM) during the presidential campaign and whose support was crucial in winning centrist votes for the new president.