The Slovenian came home 92 seconds ahead of Igor Anton as Katusha enjoyed a UCI Europe Tour double on Saturday following Rudiger Selig's victory in the Volta Limburg Classic.
Spilak was part of an early 12-man escape group that also featured Jesse Anthony (Team Optum), Igor Merino and Mikel Landa (Euskaltel-Euskadi), Cristiano Salerno and Rohan Dennis (Cannondale), Wilson Marentes (Colombia), Karol Domagalski (Caja Rural), Juan Chamorro and Ever Rivera (472-Colombia), Benat Intxausti and Javier Moreno (Movistar).
They led by over eight minutes after 67km of the race which loops through the city of Estella-Lizarra, in the Spanish region of Navarre.
The race includes several challenging climbs and inside the final 70km, Spilak along with Benat Intxausti (Movistar) and Rohan Dennis (Garmin-Sharp) went ahead.
Spilak then attacked inside the final 40km on the Lezaun climb and came home comfortably clear for his first victory since winning the 2010 Tour of Romandie.
Anton was a distant second ahead of Peter Stetina and Alejandro Valverde.
“I’m very happy of this win, it’s a pleasure to encore Moreno last year’s triumph and it’s a double satisfaction because it’s my first victory in Katusha," Spilak said in reference to team-mate Daniel Moreno's triumph in the race last year.
"I think it was a spectacular race: I was in a great shape, and when I saw my rivals in the breakaway were running out of fuel I tried by myself and I managed to take this solo win. Thanks to all my team-mates, they were great: especially Kolobnev who crashed with no serious consequences in the final part.
"Today Katusha took two great wins and I’m so happy about this. I think we can thank and the whole management of the team and the project, especially Igor Makarov, who did everything possible for our team to be here – in the season, among the best teams and with a number of great victories."