Barca's all-time top scorer Messi broke the deadlock in the 32nd minute at the Nou Camp with an immaculately struck free kick, curling the ball over the wall and right into the top near corner.
It was his second free kick goal in three home games this season.
Coached by former Barca and Netherlands midfielder Mark van Bommel, PSV had produced an admirable performance in their first visit to the Nou Camp in 21 years until they began to tire late in the second half.
The Spanish champions began to demonstrate the gulf in class as the second half progressed and they doubled their lead in the 75th minute through a lovely curling strike from in-form French forward Ousmane Dembele, who scored a fifth goal from sixth games in all competitions this season.
Barca lead Champions League Group B on goal difference after Inter Milan beat Tottenham 2-1.