Veterans Dani Alves and Jordi Alba headlined the changes from the Catalans' victory over Napoli in the UEFA Europa League on Thursday, with Gavi preferred ahead of Frenkie De Jong.
It was an overwhelming opening for the Blaugrana, which had the visitors nearly profiting from a defensive mix-up before launching efforts from Gerard Pique and Gavi that missed target.
To that end though, the Catalans took control and could’ve gone ahead on 32 minutes through a half-volley from a tight angle by Ferran Torres but Unai Simon saved.
Barca scrapped their inefficiency five minutes later as a header from Pique from a corner-kick hit the woodwork and fell to Pierre-Emerick Aubameyang to tuck home.
With the host energised by the lead heading to halftime, Bilbao saw little joy and opted for a double change at the restart in Oihan Sancet and Inigo Martinez.
Barcelona allowed a clear chance to go astray midway in the second half when Torres won a stray pass to go clear and get a shot away only for Simon to produce a point-blank save.
The former Manchester City striker was replaced 67 minutes in for Ousmane Dembele, and the latter doubled Barca’s tally after he dropped a shoulder wide of the area to smash the roof of the net.
Marcelino’s men didn’t feel helpless over five minutes from time and almost pulled a goal back through a powerful drive outside the area from Inaki Williams, which Marc-Andre Ter Stegen saved.
However, Barcelona put the clash to bed in the final minute when a teasing cross right of the area by Dembele saw Luuk De Jong attack and head home.
The Blaugrana weren’t done and bagged a fourth goal with the last kick of the game as Memphis Depay dropped into the area to side-foot in a smart supply to send Barcelona into fourth spot.