In 2017, Gilbert became the third rider after Eddy Merckx (1975) and Jan Raas (1979) to win both the Tour of Flanders and the Amstel Gold Race in the same year.

That did not stop him from trying himself during Milan–San Remo, where he managed to escape on the Poggio with Riccardo Riccò before being captured 1.2 kilometres (0.75 miles) from the finishing line.

A week later, he also won the prestigious Giro di Lombardia after escaping from the peloton with Samuel Sánchez, beating him to the finish by a half-length.

He then had a quadruple consecutive win: first, he won the Brabantse Pijl, then he repeated as winner of the Amstel Gold Race, breaking free on the Cauberg.

[26] In July he won the opening 191.5-kilometre (119.0-mile) stage of the Tour de France, winning by three seconds over Cadel Evans, allowing him to be the first person to put on the yellow jersey as overall leader.

In September, Gilbert won the Grand Prix Cycliste de Québec and took over the lead of the UCI world rankings with the 80 points awarded to the victor.

[28] He followed that performance two days later at the Grand Prix Cycliste de Montréal by finishing third, despite stating that he felt "no pressure" after his Quebec City victory.

[29] He would race in the October Italian classic, the Giro di Lombardia, taking eighth place after he was distanced on the final climb.

[34] His goals for his new squad were to perform highly in the Spring classics and help his team-mate Cadel Evans repeat his 2011 feat of winning the Tour de France.

[32] Neither of those came to fruition, as Gilbert's best result in the one-day spring races was third at La Flèche Wallonne, where he got deposited on the final climb by Joaquim Rodríguez who won atop the historic Mur de Huy with a slim margin of 4 seconds.

[36] He missed out on his goal to bring Evans in yellow to Paris and his best placing in a Tour de France stage was fourth.

[37] On 26 August 2012, Gilbert finally managed his first victory of the season by winning the ninth stage of the Vuelta a España after breaking away together with Rodríguez.

[39] On 23 September 2012, Gilbert won the UCI Elite Men's Road Race world championship and the rainbow jersey, ahead of Edvald Boasson Hagen and Alejandro Valverde by producing a massive surge on the final climb of the Cauberg.

[40] In 2013, Gilbert headed towards the World Championships without a single win in the rainbow jersey, in danger of his first winless season since turning professional in 2003.

[43] At the Amstel Gold Race, Gilbert could not repeat his winning ways of 2014 and came in tenth after having attacked on the final climb of the day, the Cauberg.

Later that week, in a three-up sprint finish of Belgian riders, Greg Van Avermaet (BMC Racing Team) won E3 Harelbeke ahead of Gilbert and AG2R La Mondiale's Oliver Naesen.

[52] The following week, Gilbert won the Three Days of De Panne after he attacked on the Muur van Geraardsbergen during the race's opening stage and soloed away to the victory by 17 seconds from his nearest competitor.

Three days later, he won the Tour of Flanders after a solo attack on the Oude Kwaremont and holding off the rest of the field over the remaining 55 kilometres (34 mi).

[55] In Stage 16 of the Tour de France, Gilbert was involved in a crash in a downhill section where he went over a wall, suffering lacerations and fracturing his kneecap.

Gilbert climbed back onto his bike and rode the remaining 57 kilometres (35 mi) to the finish in Bagnères-de-Luchon, earning him the Most Combative Rider award but ending his tour.

Gilbert was accused of abusing cortisone by an anonymous former Lotto teammate during his dominant period with Omega Pharma–Lotto, an allegation which the Belgian vehemently denies.