Competing in the main draw of the Champions League for the first time in 19 years, Sparta made a dream start with a breakthrough inside two minutes.
Lukas Haraslin’s initial effort was palmed away by Janis Blaswich, but only into the path of Kaan Kairinen, who swept a clinical first-time finish into the bottom corner.
That goal fuelled the hosts with confidence and they nearly added a second during a dominant opening quarter-hour, as Victor Olatunji directed a close-range header narrowly wide of the target.
Having won just four of their last 19 away matches in the tournament proper (D6, L9), Salzburg knew a positive response was needed.
Pep Lijnders’ men gradually improved as the first half progressed, with Moussa Yeo and Amar Dedic seeing a pair of efforts drift wide of the hosts’ goal.
The Czech champions remained a threat at the other end though, and they doubled their lead three minutes before half-time, as Olatunji fired a superb angled strike beyond Blaswich from Filip Panak’s hopeful long ball.
Armed with a two-goal advantage, Sparta looked determined to put the game beyond their opponents in the early stages of the second half.
A third goal duly arrived in the 58th minute when Olatunji capitalised on a mistake from Kamil Piatkowski before setting up teammate Qazim Laci for a simple finish from eight yards.
That all but ended the Red Bulls’ hopes of a comeback, as Iron Sparta came close to adding a fourth through substitute Ermal Krasniqi.
Desperate to restore some pride late on, Salzburg went in pursuit of a consolation, but the hosts’ rearguard ultimately held firm to secure a first victory in the main draw of the Champions League since 2003.
As for Lijnders’ side, they’ll be keen to kickstart their campaign against Stade Brestois on matchday two after a second successive defeat.
Flashscore Man of the Match: Victor Olatunji (AC Sparta Prague)