Mohamed Salah, Roberto Firmino and Divock Origi all started for Liverpool in the final third of the field, while there was a midfield position for Marko Grujic, but Sadio Mane was only on the bench, and Philippe Coutinho missed out altogether.
As for Bilbao, head coach Jose Angel Ziganda made wholesale changes following the club's Europa League commitments on Thursday night.
Inaki Williams, Mikel San Jose and Mikel Rico were selected, but the likes of Raul Garcia, Oscar de Marcos, Iker Muniain and Aritz Aduriz were absent as fringe players Inigo Cordoba, Ager Aketxe and Unai Nunez had the chance to impress.
A bright first 10 minutes saw both teams threaten in the final third, with the offside flag just denying Bilbao's Williams, before Salah curled a decent effort over Kepa Arrizabalaga's crossbar down the other end of the field.
Origi had the game's first serious opportunity after breaking into the Bilbao box, but the forward could only turn wide of the post after being found by a cute Firmino pass, before heading a Salah cross wide in the 17th minute.
Liverpool were ahead in the 21st minute, however, when Firmino scored from the penalty spot after the Brazilian had been brought to the ground by a clumsy challenge from Bilbao defender Inigo Lekue.
Bilbao should have been level in the 27th minute when Williams slid a super pass into the path of Aketxe, but the Spaniard turned his effort wide of Simon Mignolet's pass as Liverpool survived a dangerous moment.
The La Liga outfit were level on the 30-minute mark, however, when Williams took advantage of a poor mistake from Dejan Lovren to slide the ball into the bottom corner of the net.
Liverpool had a brilliant chance to regain the lead in the latter stages of the first period when Alberto Moreno broke into the Bilbao box, but the Spaniard could not beat Kepa as the score remained 1-1 at the half-time break.
Liverpool boss Jurgen Klopp made 10 changes at the interval, with Mignolet the only player to keep his spot from the first period. Among those to enter were Mane, Dominic Solanke and Andrew Robertson, while Jon Flanagan took the captain's armband.
Cordoba should have sent Bilbao 2-1 ahead in the 52nd minute after being played through by Williams, but the number 30 could not beat Mignolet, who stood tall to make a smart save, before Kepa made a wonderful stop to keep out a close-range Mane strike down the other end of the field.
Liverpool were back ahead just before the hour, however, when Ben Woodburn collected a cross from Solanke before curling the ball into the far corner of the net.
The Reds then had their third in the 79th minute when Solanke headed a super Ragnar Klavan cross into the far corner as the Premier League club ended their pre-season campaign with a comfortable win.
Next up for Bilbao is their final pre-season friendly against Deportivo Alaves on Saturday, while Liverpool will open their 2017-18 Premier League challenge away to Watford on the same day.