The Spaniard accelerates near the top of the Mur de Huy and holds on for the victory.
The podium after the midweek race mirrors that of last weekend's Amstel Gold Race.
Australian Rohan Dennis (BMC) won the second stage of the Tour of the Alps, which was shortened by 40km due to heavy snowfall on Tuesday.
Sarah Hammer rides to her 15th career world championship medal in points race behind Britain's Elinor Barker.
Belgian Philippe Gilbert outsprinted 2015 winner Michal Kwiatkowski of Poland to capture his fourth Amstel Gold win in a tactical finale.
Olympic champion Anna van der Breggen claimed her first win wearing Boels-Dolmans colors at the women's Amstel Gold Race on Sunday.
American Chloe Dygert won her first individual world title by a whopping 7.143 seconds in the women's individual pursuit.
The American women's team pursuit squad wins its second championship in a row at Hong Kong track worlds.
Italian Sonny Colbrelli wins the hilly midweek Brabantse Pijl race, out-sprinting defending champion Petr Vakoc.
Greg van Avermaet overcame a mid-race crash to claim his first 'Monument' race in a dramatic sprint victory at Paris-Roubaix on Sunday.