And soon after the Argentine had his 301st goal for the Catalans as he curled home a sumptuous free-kick to extend Barca's lead at the top to 15 points over Atletico Madrid.
Granada had won their last two games including a 1-0 home win against Real Madrid.
Iniesta restedBarca assistant manager Jordi Roura had taken the opportunity to rest Andres Iniesta ahead their Champions League tie with AC Milan in midweek, whilst Xavi was again missing through injury. But despite being without either of their two midfield metronomes Barca started brightly.
Messi was unsurprisingly to the fore and he slipped in Alexis Sanchez after just five minutes but the Chilean's heavy touch allowed Tono in the Granada goal to collect.
Thiago then headed over and Messi nearly connected with Cesc Fabregas' knockdown at the end of a wonderful move as Barce continued to dominate, but they were rocked when Granada took the lead on 26 minutes.