The BayArena played host to a meeting between two teams who have been cautiously tipped to be involved in the title race.
After dismantling Bayern Munich in the DFL-Supercup last week, Leipzig were keen to carry their momentum into this encounter, but early efforts were restricted to Benjamin Henrichs’ long-range strikes that Lukas Hradecky had covered.
Xabi Alonso’s side bided their time before threatening, but when they eventually found an opening, they made no mistake.
Victor Boniface marked his debut with an assist, superbly holding the ball up before cutting back to find Jeremie Frimpong on the six-yard line, and the wing-back couldn’t miss.
Unlike versus Bayern, Leipzig now looked shaken and had no answer for Bayer’s power as they fell two behind.
Jonas Hofmann’s looping cross from the left was met by an unmarked Jonathan Tah to bury and leave Marco Rose’s men on the ropes.
After taking advantage of some charitable defending, the hosts returned the favour and were punished before the break.
David Raum’s in-swinging corner was flicked on at the near post by Dani Olmo, and the Spaniard’s effort evaded everyone for his fourth strike in two matches.
Leverkusen were intent on quashing Leipzig’s hopes of staging a comeback, and they came so close to re-establishing their two-goal lead through Florian Wirtz, but his near-post effort was brilliantly denied by Janis Blaswich.
The 20-year-old was more ruthless shortly after the hour mark though as, after being picked out by Frimpong, Wirtz struck his shot into the ground, allowing it to bounce up and loop over the despairing Blaswich.
Leipzig were unwilling to lie down, however, and forced a way back into the contest. Mohamed Simakan rose highest to meet a free-kick and steer across goal where Lois Openda was waiting to tap in on his Bundesliga debut.
The Belgian was then presented with a glorious chance to level the contest moments later, but incredibly, he failed to convert from point-blank range with the goal gaping, instead thundering his effort against the post.
That miss proved very costly, as the opponents recorded a second consecutive victory in this fixture - they’re the only side to beat Leipzig in their last nine Bundesliga matches.
Flashscore Man of the Match: Jeremie Frimpong (Bayer Leverkusen)
In the other results of the afternoon:
Augsburg and Borussia Monchengladbach played out a blockbuster 4-4 draw in the Bavarian sunshine as Stuttgart put five goals past a sorry Bochum side in their opening match of the season.
Elsewhere, Freiburg defeated Hoffenheim 2-1 away to start their league campaign on the right foot while Wolfsburg beat Bundesliga first-timers Heidenheim 2-0.
