The Argentinean international put Barcelona into a commanding three-goal lead before Helder Postiga pulled two goals back shortly before half-time.
Barcelona were looking to exert their typical brand of possession-based dominance from the outset, especially after a lacklustre performance during their midweek Super Cup win against Atletico Madrid.
Cesc Fabregas attracted criticism for his frustrating display at the Nou Camp but he was instrumental in providing the ingredients for Messi’s hat-trick.
In the 11th minute, Sergio Busquets threaded the ball through to Fabregas who then fed Messi before he bundled the ball past Diego Alves and poked into any empty net.
They had to wait until the 39th minute for double their advantage but it was the same combination that proved pivotal. Busquets robbed Ever Banega on the halfway line, which allowed Fabregas to steer the ball to Messi who drove into the box and fired into the bottom corner.
Two minutes later Messi claimed his hat-trick, this time sweeping the ball into the far corner following Neymar’s pinpoint cut-back. The goal put the visitors in complete control and help silenced those who had suggested the South American duo are unable to function together.
However, Postiga bought the Mestalla to life with a spectacular acrobatic volley from Joao Pereira’s pacey cross. Moments later, the striker nipped in at the near post and flicked Benaga’s corner beyond the despairing reach of Victor Valdes.
After an exhilarating opening 45 minutes, Barcelona were keen to restrict a rejuvenated Valencia and frustrated the hosts for large portions of the second-half.
Messi appeared to have left his shooting boots in the dressing room at half-time after scuffing two chances straight into the grateful arms of Alves and Pedro somehow failed to hit the target when Iniesta picked him out all alone in the area.
With ten minutes remaining the game exploded back into life. Messi grazed the post after a wonderful series of exchanges with Neymar before Jonas’ saw his curling effort tipped onto the woodwork by Valdes.
Alves then ensured a tense finish for the defending champions when his remarkable double save denied substitute Jonathan dos Santos and Messi, but Barcelona held on to maintain their perfect start to the season.
It was the perfect response for Barca after Isco continued his impressive start to life at Real Madrid earlier in the day, bagging a double in a 3-1 Liga win against Athletic Bilbao.
Atletico Madrid made it three wins in three in La Liga with a 2-1 success at Real Sociedad.
David Villa fired Atletico ahead in the 27th minute at Sociedad's Anoeta stadium and set up Spain team mate Koke to make it 2-0 in the 57th before Xabi Prieto pulled a goal back for the Basque side with just over 20 minutes left.
Atletico's Belgian goalkeeper Thibaut Courtois denied Sociedad's an equaliser with a stunning reflex save in the 89th minute and another fine stop in the first minute of added time.
Espanyol and Real Betis played out a 0-0 draw while Sevilla and Malaga also share the spoils in a more entertaining 2-2 match.