Poland international Lewandowski arrived at the Bundesliga giants from Lech Poznan in 2010 and has established himself as one of the best strikers in the world during his time at Dortmund.
The 25-year-old - who has scored 72 Bundesliga goals during his time at the club - will now bid farewell to the home supporters when Dortmund host Markus Gisdol's men, ahead of his free transfer to rivals and Bundesliga champions Bayern Munich.
Dortmund head coach Klopp harbours no ill-feeling towards the forward however, and says he leaves the club a "world-class" striker.
"He arrived as a great striker and leaves as a world-class striker," Klopp said at his pre-match press conference.
Lewandowski will play for Dortmund twice after Saturday's encounter, firstly in the club's last Bundesliga fixture at Hertha Berlin before he faces his future employers in the May 17 final of the DFB-Pokal.
"Lewandowski has been a brilliant striker for us and it's been a great time," Klopp added. "I hope he gives it everything in his last 3 games."
Dortmund head into the encounter protecting a seven-match unbeaten run in Germany's top flight, and their fine run has left Klopp's charges wondering what might have been had they not suffered such a horrendous injury crisis in defence this season.
They still sit 19 points behind already-crowned champions Bayern Munich in second, but will see full-back Marcel Schmelzer return from a groin injury, while Erik Durm (ankle) could also come into contention.
However, captain Sebastian Kehl (hamstring) and fellow midfielder Oliver Kirch (illness) will miss out.
Dortmund's recent upturn in form is sure to be tested by a Hoffenheim side that have performed admirably in the Bundesliga this season.
Hoffenheim only preserved their top-flight status after winning at Dortmund in the final league game of last season, before beating second-tier Kaiserslautern in the relegation play-off.
Gisdol's men have had a far more comfortable campaign this time around and, with just two games remaining, appear set to clinch a top-10 finish.
They currently sit ninth, but forward Anthony Modeste - who has 12 league goals this term - will miss out for Hoffenheim through suspension.
‘After Manchester City’s recent form, maybe they’re the underdogs against Manchester United!’ Former Red Devils defender on this weekend’s derby
‘Arteta, Alonso, Emery, me… none of us were physical players – we needed the understanding of the game. That probably helped us move into management’: Premier League boss reveals reasons for natural career progression
