The 34-year-old Poland forward demonstrated his value by making it eight goals in five games since leaving Bayern in July.
Lewandowski, who helped Bayern win the competition in 2019-20, marked his first Champions League appearance for Barca with a clinical finish which doubled the lead after Franck Kessie had headed the hosts ahead.
He then made it 3-1 on the stroke of half-time with a header after Ousmane Dembele did well to win back possession before producing a fine cross.
Viktoria Plzen had briefly given their travelling fans from the Cech Republic something to cheer when Jan Sykora headed past Marc-Andre ter Stegen, but Barca – and Lewandowski – proved far too strong.
