With Ousmane Dembele suspended by the club following his refusal to train amid transfer speculation linking him with a move to Barcelona, it was fellow youngster Pulisic who stepped up to the mark for Dortmund.
Having already caused havoc down the right flank, the 18-year-old - who netted in the DFL-Supercup against Bayern Munich - thumped Dortmund into the lead 22 minutes in.
Marc Bartra was quick to follow suit with an equally stunning effort - his audacious cross-cum-shot putting Bosz's side well in control.
Andries Jonker's men did look to mount a comeback, Mario Gomez squandering a gilt-edged chance, but Pulisic's influence soon paid dividends again as he teed up Pierre-Emerick Aubameyang on the hour.
Although Gomez saw a goal disallowed, Wolfsburg never really threatened, as Dortmund eased to an impressive victory in Bosz's Bundesliga debut.
Despite dominating possession, Dortmund should have found themselves behind 12 minutes in.
Daniel Didavi's deflected effort led to a corner, from which Yannick Gerhardt was afforded the freedom of Dortmund's area, only to send his header well wide.
Gerhardt's wastefulness could have been swiftly punished, but Gonzalo Castro failed to apply the finish from Pulisic's wicked cross.
Bosz did not have to wait much longer for the first Bundesliga goal of his tenure, though - Pulisic engineering space on the edge of Wolfsburg's area before drilling a venomous finish past Koen Casteels.
Dortmund wasted no time in extending their lead, Bartra's sublime effort looping over Casteels and into the top right corner from an acute angle to make it 2-0 five minutes later.
Wolfsburg's misery was nearly compounded prior to the interval, Aubameyang slicing his strike just wide as Dortmund looked to wrap up the points early.
Mario Gotze, starting for the first time in 2017, was the next to try his luck, though his tame strike was dealt with comfortably by Casteels.
Gomez cut a frustrating figure for much of proceedings, although Wolfsburg's forward should have done better after shirking off Bartra's challenge to get one-on-one with Roman Burki.
Aubameyang made no such mistake at the other end, however, as last season's top scorer in the Bundesliga latched onto Pulisic's terrific cross to open his account for 2017-18.
The hosts thought they had snatched a consolation through Gomez late on, but the linesman's flag denied the former Bayern Munich man as Dortmund cruised to a fifth successive win over Wolfsburg.
Key Opta stats:
- Nuri Sahin made his 252nd appearance in a competitive game for Dortmund, levelling with club legend Manfred Burgsmüller.
- Wolfsburg have suffered heavy defeats in their last two games with referee Robert Hartmann – and both came against Dortmund (1-5 and 0-3).
- Lukasz Piszczek now holds the record for the most Bundesliga appearances (249) by a Polish player, ahead of Tomasz Waldoch (248).