Luis Suarez had the ball in the back of the net in the 11th minute after going through on goal but the Barca striker's was adjudged to be offside.
Paco Alcacer could not continue with the match in the 23rd minute after going down injured and was replaced by Aleix Vidal.
Suarez found the breakthrough for the home side in the 28th minute after Lionel Messi beat the offside trap and laid a pass off to the Uruguayan who could not miss from close range, 1-0.
Messi smashed the top corner of the crossbar seven minutes before halftime with thunderbolt following a counter-attack.
Three minutes before the break, Messi slalomed past a few players before going through on goal and hit the post but Paulinho stayed onside to poke home the second goal for Barça from the rebound, 2-0.
Suarez got his second goal in the match and a third for the hosts two minutes after halftime with a composed strike at the near post, 3-0.
On the hour mark, Ernesto Valverde took off Iniesta as Andre Gomes made his way onto the pitch for the final 30 minutes.
Barça were awarded a penalty in the 70th minute after Suarez was brought down inside the area. Messi stepped up and went for power instead of placement and his effort was saved.
Paulinho made it 4-0 five minutes later with a similar goal he scored in the first half after Jordi Alba's shot came off the post.
Barça were cruising with five minutes left to play as Messi continued to push for a goal but luck was not on his side.
In the end, 4-0 was how the score remained as Barca moved six points clear of Atletico Madrid.