Bayern trailed 1-0 at half-time, when Lewandowski came on for Thiago Alcantara.
It proved to be an inspired move, as the Poland striker scored just six minutes later to start his record-breaking haul as he demolished the Wolfsburg defence.
Lewandowski added four more in quick succession to record the fastest five goals scored by one player in Bundesliga history.
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“I am very happy, that was crazy,” said Lewandowski.
“We were 1-0 down when I came on and I knew we had to give some gas, but it’s unbelievable to get five goals.”
It was his best haul since scoring all four for ex-club Borussia Dortmund in their 4-1 win over Real Madrid in the 2013 Champions League semi-finals.
The win sees Pep Guardiola’s Bayern go top of the table, three points clear of Borussia Dortmund, who played Hoffenheim on Wednesday. Wolfsburg remain third.