New summer signing Franck Kessié headed home to open the scoring, before Lewandowski — who joined the Spanish giants from Bayern Munich during the transfer window — found his scoring touch.
The 34-year-old bent home a delightful first goal from the edge of the box before Jan Sykora headed past Marc-Andre ter Stegen on the stroke of halftime to give the Czech champions a glimmer of hope.
However, Lewandowski shut that door just minutes later, his diving header at the back post reinstating Barça’s two-goal lead as the first half ticked away.
Midway through the second half, the Polish striker had his first hat-trick for his new club when — in a mirror image of his first goal — he curled past the despairing Jindřich Staněk in the Plzen goal.
Ferrán Torres wrapped up a successful afternoon for Barça manager Xavi as he blasted home from Ousmane Dembélé’s delightful chip.
Lewandowski’s hat-trick makes him the first ever player to score a Champions League hat-trick with three different clubs — Borussia Dortmund, Bayern and now Barça. He is also just the ninth player to score a hat-trick on their Champions League debut with a club.
Afterwards, Xavi called Lewandowski “insatiable” for goals.
“The way he trains, the way he helps the team, his humility, his work-rate… I can’t praise him enough because it’s not just about his hat-trick, it’s the way he works, how he knows to dominate the tempo of the game,” Xavi said.
He added: “It was a complete game, we dominated them. They defended well, they man-marked us but Dembélé was brilliant and Lewandowski made the difference. We were the superior team and I’m delighted with the players who came off the bench as well as those who started. Everyone was really up for it.”
The hat-trick performance continues Lewandowski’s hot start to life in Spain; the striker has now scored eight goals in his first five games.
It also is the perfect warm up for Lewandowski’s return to face Bayern in next week’s Champions League clash between his new and old clubs.
Lewandowski joined the Catalan giant for $46.1 million plus $5.12 million in additions in July having scored 344 goals in 375 appearances for Bayern, second most for the club behind Gerd Müller.
At the death
In Madrid, Wednesday’s most dramatic game was taking place between Atlético Madrid and Porto as three goals after the 90th minute provided a thrilling end at the Metropolitano Stadium.
A stodgy regular time concluded with Porto being sent down to 10 men after Mehdi Taremi was shown his second yellow card for diving.
Atlético defender Mario Hermoso’s looping shot in the 91st minute looked to have settled the tie, only for Porto to be awarded a penalty in the 96th minute after Hermoso was deemed to have handled the ball.
Mateus Uribe converted from the spot to level the scores, but the drama was not over there.
As the clock ticked into three digits, Antoine Griezmann nodded home from close range in the 101st minute to spark wild scenes of celebration, with Atleti manger Diego Simeone running to celebrate with his players.
“It’s was difficult [for us] to get into the game, create chances,” Griezmann said afterwards. “The pace of the game was slow and we needed to put some extra intensity into it and, in the end, we did it in the last minutes.”
It is only the second time in Champions League history where there have been three goals in the 90th minute or later, excluding extra time. Oddly enough, the first time it happened was a fixture between the two same teams last December.