The Germany global has been sidelined since January 29 after club medics discovered he was suffering with a metabolic disorder.
Mario Gotze set up the opening goal in his first start in nine months as Borussia Dortmund began the Bundesliga season with a stylish win at Wolfsburg.
The absence of suspended Ousmane Dembele, who missed training last week amid speculation about a possible move to Barcelona, was quickly forgotten as Marc Bartra doubled the lead five minutes later against a dazed Wolfsburg defence.
Wolfsburg's Mario Gomez, left, and Dortmund's Marc Bartra vie for the ball during the German Bundesliga soccer match between VfL Wolfsburg and Borussia Dortmund in the Volkswagen Arena in Wolfsburg, Germany, saturday, August 19, 2017.
It was the flawless start for new manager Peter Bosz, who left Ajax to replace Thomas Tuchel earlier this summer.
With the Wolves cornered, Dortmund kept up the pressure and Pierre-Emerick Aubameyang, last season's Bundesliga top scorer, added a third on the hour.
"I'm really happy, both for us and for Mario, that he's able to play again straight away", Dortmund sporting director Michael Zorc told Sky before the game. "Overall we delivered a very good team performance and that is important". "Not only because of the goal".
The highlight was his equaliser in Borussia's 2-2 draw with Real Madrid in the group stages of the Champions League.
Elsewhere, Mathew Leckie scored twice on his league debut for Hertha Berlin to beat promoted Stuttgart 2-0 at home.
Pulisic scored three times and made six assists in 29 appearances in the Bundesliga last term.