The Movistar rider was at the front of the peloton as it reached the final 200m climb at the end of the 194km route from Charleroi to Huy.
And the Spaniard then made his move, powering up the hill and beating Daniel Martin (Garmin-Sharp) and Michal Kwiatkowski (Omega Pharma - Quick-Step) into second and third respectively by three seconds.
It is the second Fleche Wallone victory of Valverde's career, and confirms his status as one of the favourites for the Tour de France.
Despite the peloton setting a frenetic pace in the opening stages, three riders – Jonathan Clarke (United Healthcare), Preben Van Hecke (Topsport Vlaanderen-Baloise) and Ramunas Navardauskas (Garmin-Sharp) – managed to pull clear.
The trio’s lead stretched to nine minutes before BMC and Katusha combined to drag the peloton back into contention, quickly catching the weary Clarke and overhauling the other two escapees with 12km remaining.
With the group charging towards Huy, Jeremy Roy darted for the finish line from distance only to see his move snuffed out by an increasingly strained front pack.
A late crash scuppered pre-race favourite Philippe Gilbert’s chances as the peloton was unsettled in the closing stages, leaving Valverde in prime position for the final assault.
1. Alejandro Valverde (Spain / Movistar) 4:36:45"
2. Daniel Martin (Ireland / Garmin) +3"
3. Michal Kwiatkowski (Poland / Omega Pharma - Quick-Step) +4"
4. Bauke Mollema (Netherlands / Belkin) +5"
5. Tom-Jelte Slagter (Netherlands / Garmin) +6"
6. Dennis Vanendert (Belgium / Lotto)
7. Michael Albasini (Switzerland / Orica) +8"
8. Roman Kreuziger (Czech Republic / Tinkoff - Saxo) +9"
9. Daniel Moreno (Spain / Katusha) +11"
10. Philippe Gilbert (Belgium / BMC Racing) +15"
- Sports & Recreation
- Daniel Martin
- Michal Kwiatkowski
- Omega Pharma
- Alejandro Valverde
- Preben Van Hecke