2015–2019

After an uneventful season with Omega Pharma–Quick-Step, De Gendt moved to Lotto–Soudal in 2015 on an initial two-year contract.^[26] In his first season with the team, De Gendt won the mountains classification at Paris–Nice,^[27] and following Stefan Denifl's results being expunged in 2019, was retroactively designated the winner of the mountains classification at the Tour de Suisse.^[28]

At the 2016 Volta a Catalunya, De Gendt led the sprints classification from start to finish, and he also won the mountains classification,^[29] having assumed the lead after his stage victory on stage four,^[30] the queen stage of the race. At the Tour de France, De Gendt held a jersey for the first time at a Grand Tour, taking the polka dot jersey as mountains classification leader following stage five – where he had finished second to Greg Van Avermaet.^[31] He held the jersey for three stages initially, and then regained the lead for a further three days following stage twelve, after winning on Mont Ventoux.^[32] He ultimately finished second to Rafał Majka in the mountains classification standings.^[33]

In his first start of the 2017 season, De Gendt won the mountains classification at the Tour Down Under, taking the jersey from Richie Porte on the final day of the race.^[34] He won the opening stage of the Critérium du Dauphiné, over a hilly route in and around Saint-Étienne; he soloed clear of his breakaway companions and won the stage by approximately 45 seconds.^[35] He held the race lead through until stage six, when he lost more than eight minutes to the stage winner, Jakob Fuglsang.^[36] At the Vuelta a España, De Gendt won stage 19 from a breakaway, completing his set of stage wins in all three Grand Tours.^[37]

In 2018, De Gendt won the mountains classification at Paris–Nice,^[38] having taken the lead on the penultimate stage of the race. In his next start, he won the third stage of the Volta a Catalunya after a solo attack of around 50 kilometres (31 miles); he took the race lead by 23 seconds following the stage,^[39] but he would cede the lead the following day, losing 24 minutes.^[40] He added to his string of long breakaway victories by winning the second stage of the Tour de Romandie in solo fashion.^[41] He would ultimately go on to win both the points and mountains jerseys at the race.^[42] He finished second in the Belgian National Time Trial Championships in June, losing out to teammate Victor Campenaerts by a margin of three seconds.^[43] At the Vuelta a España, De Gendt won the mountains classification,^[44] having taken the lead on stage 17 from Luis Ángel Maté,^[45] who had held the lead of the classification from the start of the race.

Just as he did in 2018, De Gendt won the mountains classification at the 2019 Paris–Nice,^[46] his third such victory in five years, having taken the jersey on stage four when he finished second to Magnus Cort on the stage.^[47] He then won the opening stage of the Volta a Catalunya, winning the stage by almost three minutes after a solo move of some 60 kilometres (37 miles), attacking from a six-man breakaway group.^[48] He held onto the overall race lead until stage four,^[49] but was able to hold onto the mountains classification lead throughout the race. At the Tour de France, De Gendt took his second career stage win,^[50] winning the eighth stage of the race from the breakaway; he attacked on the final categorised climb – the Côte de la Jaillère – dropping Alessandro De Marchi,^[51] and he then held off Thibaut Pinot and Julian Alaphilippe to win the stage by six seconds.^[52]

2020 onwards

After a winless 2020 – impacted due to the COVID-19 pandemic – De Gendt took his fifth Volta a Catalunya stage victory on the final stage of the 2021 edition,^[53] spending more than 100 kilometres (62 miles) in the breakaway, before attacking with approximately 5 kilometres (3.1 miles) remaining.^[54]

At the 2022 Giro d'Italia, De Gendt took his first stage victory at the race for a decade,^[55] winning a hilly stage in and around Naples; he was part of a four-rider move that broke away from a larger breakaway group with approximately 40 kilometres (25 miles) remaining, and was assisted by his teammate Harm Vanhoucke in the final sprint to the line.^[56] That July, De Gendt signed a two-year contract extension with Lotto–Soudal, until the end of the 2024 season.^[57]