Del Bosque's side hits five in an impressive performance against disappointing South American opposition, with the Valencia front man the star.
Roberto Soldado marked his first appearance for Spain since 2007 with a clinical hat trick, while David Silva and Andres Iniesta were also on the score sheet as the home side dominated its less illustrious opponent.
Home goalkeeper Iker Casillas was forced into making an early save from Venezuela's Salomon Rondon after the striker hit an instinctive shot towards goal from the left side of the penalty area.
Spain was then denied by the crossbar in the sixth minute when Sergio Ramos planted a header against the frame of Dani Hernandez's goal. The Real Madrid center-back had the chance after being set up beautifully by Silva following a short corner on the right.
Iniesta very nearly gave the home side the lead after latching on to an incisive ball from Cesc Fabregas and striking a firm effort at goal. However, Dani was a match for the strike and did well to parry the ball to safety.
As the first half wore on it became clear from the whistling that, despite it being a friendly, the home fans expected goals from their side against a team ranked 46th in the world.
The Spain players appeared to sense the fan frustrations and responded accordingly by scoring twice in quick succession. The breakthrough came in the 37th minute courtesy of a neat finish from the edge of the box by Iniesta, after he was found in space by a slick pass from his Barcelona teammate Fabregas.
Silva added a second for the home side just minutes later with a crisp strike from 20 yards after Fabregas had set him up with a nonchalant back heel.
Much of the talk before the game surrounded Roberto Soldado's inclusion in Vicente del Bosque's squad following his scintillating form for Valencia this season, and it took the striker just five minutes to leave his mark on the game.
After being introduced at halftime, Soldado scored Spain's third of the evening on 50 minutes, turning in Santi Cazorla's cross after some sumptuous build-up play on the edge of the Venezuela penalty area had set the Malaga playmaker free inside the box.
Soldado seemed intent on marking his reintroduction to the national setup in style and grabbed another goal just two minutes later with a confident finish from close range after an inch perfect cross from the right side by Alvaro Arbeloa.
To make matters worse for the away side, it was then reduced to 10 men when Fernando Amorebieta was given a red card for hauling Soldado down inside the penalty area, providing the striker with the opportunity to seal a fairytale hat trick with a goal from the spot.
Soldado's kick was weak however, with Dani diving low to his right to divert it to safety, much to the forward's despair.
Iker Muniain made his debut midway through the second half, replacing Cesc Fabregas, and the diminutive Athletic Bilbao player came close to scoring just minutes after entering the fray, testing Dani with a stinging effort.
Soldado finally completed his treble, with a close range finish after fine work down the left from his club teammate Jordi Alba set up the chance.
It turned out to be a comfortable victory for Spain, and a fantastic return for Soldado after five years in the international wilderness.
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