Roberta Mezzola, a Maltese, is the third woman to preside over the European Parliament after French women Simone Veil (1979-1982) and Nicole Fontaine (1999-2002).
Mitsula is 43 years old, making her the youngest person to head the European Parliament.
Mitsula, a conservative, presents herself as a progressive, supportive of LGBT issues and a campaigner for women's rights, but her anti-abortion stance has drawn criticism from opponents.
While abortion is illegal in Malta, where most of the population is Catholic, Mitsula voted against a report urging all member states of the European Parliament to provide safe access to abortion.
European Commission President Ursula von der Leyen congratulated Mitsola, writing on Twitter, "As the third woman to preside over this noble council, your hard work and determination are an inspiration to us all."
Ursula continued, "We will work closely together for the recovery of the European Union and a bright, green, digital European future."
Mitsola stressed that combating climate change will remain a priority for the European Parliament, calling on MEPs to adopt reforms to make the parliament's role more important.