David Villa kept up his good scoring record against Real as he netted his seventh goal in nine games against the Basques with only eight minutes on the clock.
Andres Iniesta made it two 13 minutes before the break, Messi struck at either end of the second half and substitute Bojan Krkic made it five at the death.
"The advantage I have over everyone else is that I get to see the team every day in training and how they are working. It is a privilege to work with them," said Barca coach Pep Guardiola afterwards.
"This is the year that we're playing better than ever. Also we improve with the more time we have together. I admire these guys for the consistency they are showing."