Maggie Celine Louise De Block was born in Merchtem, Province of Brabant (present-day Flemish Brabant) on 28 April 1962. She was the first of three children born to Jan De Block who worked at the Belgian railway company the NMBS/SNCB. After her first brother was born, her mother became a housewife to care for the children. When Maggie was seven her father passed away in a car accident. Five months later her mother gave birth to Maggie’s second brother who they called Jan after their father. She went to the former secondary school Koninklijk Lyceum (now Lyceum Martha Somers Brussel) in Laeken. After her graduation, she studied medicine at the Vrije Universiteit Brussel. Still a student in 1982, De Block married Luc Asselman. They have two children. She graduated as a family doctor.

In 1999 De Block nominated herself for the federal election as member of the liberal party Vlaamse Liberalen en Democraten also known as VLD. During the elections, she was elected as a Member of the Belgian Chamber of Representatives for the electoral district Brussels-Halle-Vilvoorde. De Block was an MP between 1999 and 2011. Four years after the election she became Secretary of the Chamber of Representatives for four years. In 2010 De Block also became Chairman of the Infrastructure Committee until the following year. De Block was chosen to become Secretary of State for Asylum, Immigration, and Social Integration in the newly Di Rupo Government which would be formed in December 2011. On 6 December she becomes Secretary of State for Asylum, Immigration, and Social Integration and part of the Federal Government.

In December 2012, she became the vice-chair of the Open VLD party. She later became Minister of Justice charged with Asylum, Immigration, Social Integration, and Poverty Reduction in the Di Rupo Government in July 2014.

In March 2013, she was voted woman of the year by readers of the francophone newspaper La Libre Belgique. In 2013 and 2014 polls, she became the most popular Flemish politician, ahead of the Minister-President of Flanders Kris Peeters.

In the Michel Government formed in October 2014, she became Minister of Social Affairs and Health. When taking the oath, she described the portfolio as “her dream”. Critics have said that she does not set the right example as Health Minister due to her obesity, and she has answered that “I know I’m not a model but you have to see what’s inside, not the packaging”. In the position, she was involved in coordinating the Belgian response to the Ebola virus epidemic in West Africa.

In 2015, she became the most popular politician in Flanders, Wallonia and Brussels – making her the most popular politician in Belgium.

In 2018, under her direction as health minister, the strategic reserve of FFP2 masks was destroyed because of being out of date and not replenished. DeBlock claimed she did not replenish them to save taxpayer money. This decision came under fire during the Coronavirus pandemic when the shortage of masks contributed to make Belgium one of the hardest-hit countries.

In September 2018 she decided to introduce plain packaging for all tobacco products in Belgium.

On 9 December 2018, it was announced that de Block would be responsible again for Asylum and Migration, replacing Theo Francken. She held the post in a previous government. Her official title in thecaretaker Michel II government and in the succeeding Wilmès government was Minister of Social Affairs and Public Health, and Asylum Policy and Migration.