She was confirmed by a margin of 383 votes to 327. She needed the backing of 374 out of 747 MEPs to win.
With her vision of a greener, fairer and rule-based Europe, the first female EU Commission President will replace Commission President Jean-Claude Juncker on 1 November.
She secured the backing of more than half of the members of the European parliament on Tuesday evening.
The Commission drafts EU laws, enforces EU rules and has the power to impose fines on member states if necessary.
She is further expected to tackle controversial issues such as climate change, trade and maintaining democracy in the bloc.