Los Che came close to levelling the score in the 38th minute, but Dorlan Pabon's shot was well saved by Victor Valdes. The home side had no answer for what was to come next, as Messi and Neymar terrorised the defence.
The Argentinian grabbed his second of the game just moments after Valdes's save and went on to complete his hat-trick in the 41st minute when his Brazilian teammate set him up from close range.
Just as the match was getting away from Miroslav Dukic's men, Helder Postiga set about making the Serb's half-time team talk a more positive one with two goals in quick succession - the first a stunning volley.
Messi wasted a couple of glorious opportunities to add to the score late on, but it was the post that came to Barca's rescue when Jonas had Valdes beaten in the 90th minute.