Schulze served as the Minister for the Environment, Nature Conservation and Nuclear Safety in the fourth coalition government of Chancellor Angela Merkel from 2018 to 2021.

Schulze joined the SPD in 1988[3] and served as highschool students' county spokesperson for North Rhine-Westphalia from 1988 to 1989, then as a member of the Socialist College Association and chair of the AStA at the University of Bochum.

From 2017 until 2018, Schulze served as Secretary General of the SPD North Rhine-Westphalia, in this capacity supporting interim chairman Michael Groschek.

[8] In the negotiations to form a fourth coalition government under Chancellor Angela Merkel following the 2017 federal elections, Schulze was part of the working group on education policy, led by Annegret Kramp-Karrenbauer, Stefan Müller and Hubertus Heil.

On 9 March 2018, she was nominated by the party executive committee of the SPD as Minister of the Environment, Nature Conservation and Nuclear Safety in the new government.

[10] After SPD chairwoman Andrea Nahles resigned in 2019, Schulze declined to join the race to succeed her;[11] instead Saskia Esken and Norbert Walter-Borjans became the party's co-chairs.

[12] She later oversaw the introduction of 2021 legislation under which farmers in Germany would have to gradually reduce their use of glyphosate and stop using it completely from 2024 in order to preserve clean habitats for insects.

At the time, Germany was engaging in a nuclear phaseout while experiencing an energy crisis and heavily relying on coal and natural gas for power generation.

[24] In October 2023, Schulze joined the first joint cabinet retreat of the German and French governments in Hamburg, chaired by Scholz and President Emmanuel Macron.

In a 2021 interview with RedaktionsNetzwerk Deutschland, she argued that "as a former science minister, I see patent protection as the basis for successful research and development" and that "the manufacturing process for modern vaccines is so technically demanding and complex that suspending it would not help at all.