The Movistar rider perfectly timed his attacks in the final ascent in the Mur de Huy, a 1.3km climb at an average gradient of 9.8 per cent, to add to his 2006, 2014 and 2015 titles.
Valverde was set up perfectly by his team-mate Giovanni Visconti and all that was left to do was finish off a race well suited to his considerable talents.
"The team was immense. An absolute marvel, the whole squad was amazing, in perfect harmony since this very morning," Valverde said.
"We were able to do the race we wanted to and crown it in the best possible way. Imanol, Rubén, Betancur, Rory, Dani, Visco… all of them pushed like hell and paid attention to every single split into the bunch, keeping me calm at the front."
Joaquim Rodriguez (Katusha) was the first to attack in the Mur de Huy but Valverde was alert and went with him before counter attacking Dan Martin (Etixx-QuickStep) and sprinting to victory.
Julian Alaphilippe (Etixx-QuickStep) matched his performance of last year by again finishing second with Martin coming home in third place.
"Before the last Mur de Huy there was a lot of fighting, swerving and also mind games," Valverde said. I wanted to get to the front before the real climbing started to avoid any surprises.
"Purito attacked first, Daniel Martin followed shortly after. That moment, I saw my feelings were so incredibly great that I couldn't do any other thing but going after them."
Valverde, whose main target this year is next month's Giro d'Italia, will be the hot favourite to win Liege-Bastogne-Liege, the season's penultimate Monument classic, on Sunday.
"I'm really happy, as much as willing to go for next Sunday. We've fulfilled our internal goal, which was winning Flèche, now it's time to rest up and think about Liège," Valverde said.