The newly-crowned Bundesliga champions arrived at the Aviva Stadium on a historic 51-match unbeaten streak in all competitions, felling dozens of foes in their pursuit of a treble, but it took just one former Charlton Athletic youngster to blow them to smithereens.
Xabi Alonso's meek men were second best all evening and succumbed to a tremendous Lookman treble - just the sixth time that a hat-trick has been scored in a major UEFA final - as the indomitable Italians ended their 61-year drought without another coveted honour.
Not since the 1962-63 Coppa Italia - their inaugural major trophy - had La Dea hoisted a top-level piece of silverware aloft, but Gian Piero Gasperini's men deservedly conquered the second-tier continental tournament, ending Leverkusen's hopes of achieving Invincible status in all competitions this season.
While the much-coveted talent Florian Wirtz was passed fit to start for Bayer Leverkusen, Alonso peculiarly went without a proper number nine, leaving both Patrik Schick and Victor Boniface on the bench as Jeremie Frimpong started in a more advanced area.
Electric Lookman crushes lackadaisical Leverkusen
Alonso's selection calls did not pay dividends whatsoever, as Gasperini's Atalanta BC outfit took control of proceedings from the off, suffocating the Bundesliga champions with their well-executed press.
The Italians' barnstorming start was rewarded in the 12th minute, when ex-Chelsea full-back Davide Zappacosta pulled the ball back across the six-yard box and to the back stick, where Lookman caught Exequiel Palacios sleeping, got goal-side of the Leverkusen midfielder and slotted home.
A handful of Dea coaches could not help but briefly invade the Dublin field in ecstasy, and Leverkusen's attempts to string a build-up sequence together were futile, barring a pop from semi-final hero Josip Stanisic in the 19th minute, which fell straight at Juan Musso's feet.
Normal service quickly resumed, and history was made for Lookman in the 25th minute; Leverkusen cheaply lost possession inside their own half, the Nigeria international cheekily nutmegged Granit Xhaka and found the far corner from 20 yards with aplomb.
In doing so, Lookman became the first African male player to score more than one goal in a major UEFA final, and a lacklustre Leverkusen side could not muster up a response before the break, although their affinity for astounding comebacks meant that Atalanta could not breathe easy.
Prior to their jaunt to Dublin, Leverkusen had drawn three and won one of the four games where they found themselves two goals behind this season, and the introduction of Boniface for Stanisic at half time was no shock; meanwhile, Giorgio Scalvini replaced the injured Sead Kolasinac for La Dea.
Atalanta clinch inaugural European trophy in Dublin
The lion's share of possession in the early period of the second half belonged to Leverkusen, but the German champions were still found wanting in terms of their final ball, while a succession of poor set-pieces did not help their cause either.
Credit where credit was due to Atalanta's staunch rearguard action and unwavering pressure, and as the 75-minute mark struck, Atalanta had the firmest grip possible on the crown thanks to their hat-trick hero.
Again, Leverkusen were their own worst enemies with some sloppy play inside the Atalanta half, allowing Gianluca Scamacca to lead the counter charge before the Italy striker laid off Lookman, who shifted the ball onto his left, jinked past Edmond Tapsoba and completed a terrific treble with an arrowed shot into the far top corner.
A relatively strong shout for a Leverkusen penalty in the 90th minute was turned down by the VAR room, epitomising Die Werkself's nightmarish evening in Dublin, and Lookman's blue-and-black-clad teammates launched him into the air as the full-time whistle sparked Dea delirium.
A dumbfounded Leverkusen can still end the campaign with a domestic double to their name as they prepare for Saturday's DFB-Pokal final with Kaiserslautern, while champions Atalanta have two remaining Serie A fixtures to fulfil against Torino (May 26) and Fiorentina (June 2) before the real party can commence.