A motion of no confidence against French Prime Minister Bayrou's government was supported by 364 members of the 577-seat National Assembly, forcing him to resign.
Macron's office said it would accept Bayrou's resignation on Tuesday and appoint a new prime minister to form a government in the coming days.
The new prime minister must convince members of the deeply divided lower house of parliament to reach a consensus on next year's budget by the end of December. France also faces a series of protests against public spending cuts, with demonstrations organized by the "total lockdown" movement expected to begin on Wednesday.
France's national debt has risen from €2.2 trillion (about $2.6 trillion) before Macron's election to €3.3 trillion this year, and the fiscal deficit reached 5.8% of domestic output last year. Bayrou's proposed €44 billion in spending cuts, including the cancellation of two public holidays, to reduce the deficit to 5.4%, have sparked widespread political outrage.