Van der Breggen grew up in a cycling family in Zwolle and joined her local club, WV Noordwesthoek, at seven. She qualified as a nurse in 2012 before committing to racing full time. Her wins came on short steep climbs and from attacks a long way out rather than in sprints.
She won Flèche Wallonne in 2015 and every edition after that through to 2021, always on the ramp of the Mur de Huy. In 2017 she added Amstel Gold Race and Liège-Bastogne-Liège in the same week, the first woman to win all three Ardennes classics in a season, and that Liège was the first women's edition of the race.
At the Rio Olympics in 2016 she won the road race from a three-up sprint on Copacabana ahead of Emma Johansson and Elisa Longo Borghini, and took bronze in the time trial. She attacked alone 39km from the finish at Innsbruck in 2018 for her first world road race title, then won both the time trial and the road race at Imola in 2020, a double last managed by Jeannie Longo in 1995.
Stage racing brought her the Giro Rosa in 2015, 2017 and 2020, and the Giro d'Italia Donne in 2021. She took time trial bronze at the Tokyo Olympics and stopped racing at the end of that season, aged 31. From 2022 she worked as a directeur sportif at SD Worx, calling races from the car for a team built around Demi Vollering.
She announced in June 2024 that she would race again, and returned in 2025. She won stage 4 of La Vuelta Femenina with a descent attack and finished third overall behind Vollering and Marlen Reusser. She was sixth at the Giro d'Italia Women and rode her first Tour de France Femmes, a race that did not exist in her first career. At Kigali she took world time trial silver behind Reusser.









