The two teams convene in Dublin, where Leverkusen will try to complete the second leg of an incredible treble and their Italian counterparts seek a first-ever European trophy.
Match preview
Harshly labelled 'Neverkusen' when their team of 2001-02 finished runners-up in the Bundesliga, DFB-Pokal and Champions League, Bayer Leverkusen have this year set about disproving that unwanted tag in the most improbable style.
Struggling in the bottom half of the table when Xabi Alonso took over less than two years ago, Die Werkself have since risen right to the very top, shrugging all-comers aside in the German top flight: beating Augsburg last week completed an 'invincible' 34-game league campaign.
Previously five-time Bundesliga runners-up, Leverkusen ultimately finished with 90 points on the board, ending Bayern Munich's 11-year reign of dominance and finally getting their hands on the Meisterschale.
A fluent attacking force under their highly-rated head coach, they have racked up 135 goals in all competitions this term, while conceding only 39 - yet the Rhine club can still embellish what will already go down as an historic season.
Leverkusen are looking to lift their second European trophy, following the 1988 UEFA Cup, and should they succeed in the Irish capital, then a treble will be up for grabs when Xabi Alonso and co take on second-tier Kaiserslautern in the DFB-Pokal final three days later.
In addition to an uncanny knack for staying undefeated, Die Werkself have become renowned for scoring a series of crucial late goals, and their continental adventure could have ended much earlier if it were not for a never-say-die spirit.
They trailed unfancied Qarabag 2-0 in both last-16 legs, only to fight back and progress, before stunning semi-final opponents Roma earlier this month, when Josip Stanisic supplied a 97th-minute strike to cap their comeback.
Leverkusen also overcame reigning Conference League champions West Ham United in the quarter-finals, and having previously cruised through the group stage with a flawless record of six wins from six, they could now become just the fourth team to lift the trophy unbeaten.
Atalanta's last meeting with Leverkusen came in the 2021-22 Europa League, when they won 3-2 at home before losing by a single goal one week later in Germany - but the stakes will be far higher on Wednesday evening.
Having seen off Marseille in the semis, after topping Group D and then eliminating new Portuguese champions Sporting and Premier League giants Liverpool, La Dea can dream of claiming glory in a first-ever European final.
Now the 11th different Italian team to reach a continental decider, the Bergamo club could also become the first Serie A side to win the Europa League - if they can avoid falling at the final hurdle.
Since revered coach Gian Piero Gasperini's arrived in Lombardy eight years ago, Atalanta have been transformed into regulars on the European stage, once managing a remarkable run of three Champions League qualifications in a row.
However, the 66-year-old tactician has yet to lift silverware, with his team having recently lost the Coppa Italia final to Juventus for a second time in four years, marking his third defeat overall in the cup's Rome finale.
Gasperini will walk out in Dublin as the oldest manager to take charge of his first European final, while relative newcomer Xabi Alonso is the youngest coach to lead a UEFA finalist since 2012 - the tactical battle between two very different men is sure to be fascinating.
While only Serie A champions Inter have posted a higher goals rate during the second half of the season, free-flowing Atalanta have proved rather more circumspect in continental competition, facing only 2.8 shots on target per game in the Europa League so far - the lowest ratio of any side to take part.
La Dea kept another clean sheet last weekend, when a vital victory over Roma was followed by beating Lecce 2-0: forward pair Charles De Ketelaere and Gianlucca Scamacca were on target at Via del Mare, wrapping up both a top-five finish and a cherished Champions League return.
Already a beloved figure in Bergamo, if 'Gasp' can now shake off the tag of nearly-man and help Atalanta win their first major trophy since 1963 - beating brilliant Leverkusen on the way - that would cement his status as an all-time great among fans of the Nerazzurri.
Atalanta BC Europa League form:
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Atalanta BC form (all competitions):
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Bayer Leverkusen Europa League form:
D
W
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D
Bayer Leverkusen form (all competitions):
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W
Team News
Blessed with a clean bill of health, Xabi Alonso can select freely from his Bundesliga-winning squad for the final, and there is plenty of competition for places.
Piero Hincapie and influential midfielder Granit Xhaka are set to be recalled on Wednesday, while it remains to be seen whether Victor Boniface or Patrick Schick starts up front - alternatively, a 'false nine' may be employed.
Leverkusen's Basque boss will certainly call upon star man Florian Wirtz, who has been nursed through the last few weeks with a thigh injury but made a cameo from the bench against Augsburg and should now be able to start.
The 21-year-old has recorded 18 goals and 19 assists in all competitions, and after his semi-final strike versus Roma he has already scored 11 career goals in the Europa League.
While Charles De Ketelaere, Ademola Lookman and Teun Koopmeiners all pose a threat for Atalanta, the Serie A side should entrust Gianluca Scamacca with the main striker's role in Dublin.
Having scored only once in the group phase, the Italy forward has since found the net in each knockout round, including a double in La Dea's famous win at Anfield - in all, he has six Europa League goals to his name this season.
In addition to Emil Holm, who misses out with a calf injury, experienced skipper Marten De Roon will be sidelined by a thigh strain suffered in the Coppa Italia final.
Club captain Rafael Toloi and fellow defender Sead Kolasinac are both doubts too, so Giorgio Scalvini is likely to join Isak Hien and Berat Djimsiti in the Nerazzurri's back three.
Atalanta BC possible starting lineup:
Musso; Djimsiti, Hien, Scalvini; Zappacosta, Pasalic, Ederson, Ruggeri; Koopmeiners, De Ketelaere; Scamacca
Bayer Leverkusen possible starting lineup:
Kovar; Tapsoba, Tah, Hincapie; Frimpong, Xhaka, Andrich, Grimaldo; Hofmann, Wirtz; Schick
We say: Atalanta BC 1-2 Bayer Leverkusen
Furthering their claim to be one of the greatest club teams to grace the game, Leverkusen can overcome Atalanta's thrilling mix of flair and power, as they are relentless from back to front and never know when they are beaten.