After several riders had abandoned the race due to crashes and injuries, the decisive break was formed with 30 kilometres (19 mi) to go by Sagan, Michał Kwiatkowski (Team Sky) and Sep Vanmarcke (LottoNL–Jumbo).

The racing started outside the city and took the riders southwest through Torhout to Roeselare, then east through Ardooie and Tielt, then south-east to Oudenaarde, passing across the first cobbled sector of the day, the flat Huisepontweg.

The route turned north and, following the climb of the non-cobbled Kortekeer, the riders entered a 20-kilometre (12 mi) section with several cobbled roads.

The route then turned back to the south-west, across the flat Haaghoek cobbles and then the non-cobbled climbs of the Leberg, Berendries, Valkenberg, Kaperij and Kanarieberg.

This brought the route back to take on the second ascent of the Oude Kwaremont, followed immediately by the steep cobbled climb of the Paterberg, 360 metres (390 yd) long with an average gradient of 12.9% and sections at over 20%.

[3] Additionally, there were seven sectors of flat cobbled roads:[3] The 18 UCI WorldTeams were automatically invited and were obliged to participate in the race.

"[12] The other former winners present at the start were Alexander Kristoff (Team Katusha), the defending champion, and Cancellara's teammate Stijn Devolder.

[12][13] Before the race began, there was a minute's silence in memory of Antoine Demoitié, a Wanty–Groupe Gobert rider who had been killed in a crash with a motorbike during Gent–Wevelgem.

The riders were Hugo Houle (AG2R La Mondiale), Federico Zurlo (Lampre–Merida), Imanol Erviti (Movistar), Lukas Pöstlberger (Bora–Argon 18), Gijs Van Hoecke (Topsport Vlaanderen–Baloise) and Wesley Kreder (Roompot–Oranje Peloton).

André Greipel (Lotto–Soudal) and Nils Politt (Katusha) then attacked on the Leberg and were allowed to go; they were followed by Dmitriy Gruzdev (Astana) and Dimitri Claeys (Wanty–Groupe Gobert).

Shortly afterwards, with 30 kilometres (19 mi) remaining, Michał Kwiatkowski and Peter Sagan attacked together and were joined by Sep Vanmarcke.

[15] On the final climb of the Oude Kwaremont, Kwiatkowski was unable to follow Sagan and Vanmarcke, while Cancellara rode clear of the peloton.

Kristoff won the sprint for fourth place, ahead of Luke Rowe (Sky), 49 seconds behind Sagan.

[18] Vanmarcke, meanwhile, said that he had struggled due to crashes in the middle part of the race and then had suffered cramp when Sagan attacked on the Paterberg.

[21] Luke Rowe's fifth place was Team Sky's best ever performance in the Tour of Flanders; he praised Kwiatkowski's move, but said "there's not much you can do when someone has better legs"; he described Sagan, Cancellara and Vanmarcke as "the three strongest guys in the race".

[23] Sagan remained at the top of the 2016 UCI World Tour standings following his victory; his total of 329 points was more than 100 ahead of the next rider, his teammate Alberto Contador.

[24] Sagan's total put Slovakia in third place in the nations' rankings, ahead of Great Britain and Spain, even though he was the only Slovakian to have scored World Tour points.