The Polish attacker is set to leave the club for Bayern Munich at the end of the season on a free transfer, after establishing himself as one of the deadliest forwards in Europe over the past two seasons.
BVB have already announced that Adrian Ramos will arrive from Hertha Berlin this summer, while the DFB-Pokal finalists have also been heavily linked with a move for Torino's Ciro Immobile, but Watzke is still expecting his side to miss Lewandowski.
"I would caution against the idea that we will be able to replace him completely," he is quoted as saying by the club's official website.
"There are only two or three players of his quality in the world and we can't afford them. So far we have always been able to fill the void left by top quality players."
Despite Lewandowski's imminent departure, just a year after Mario Gotze's move to Bayern, Watzke insisted that he is unconcerned by rumours that ace attacker Marco Reus and coach Jurgen Klopp could also be lured away from Signal Iduna Park.
"It's not a surprise that our players are moving into the focus of top European clubs," the Dortmund CEO explained. "We know what we have in Marco.
"I'm quite sure that Marco likes it here with us very much and knows what he has at this extraordinary club. I'm sure that Marco will celebrate more successes with BVB.
"We are very pleased about the way Klopp and Mats Hummels have expressed their commitment to BVB again and again in the last couple of weeks.
"That shows that we on a path where sporting ambitions can be realised."