Catalytic depolymerization of lignin is a challenging process due to competitive repolymerization reactions. In this paper, the oxidative depolymerization of lignin was catalyzed by a commercial laccase both in a batch experiment and in a membrane bioreactor using the same catalytic conditions. The membrane bioreactor was previously optimized to reach high permeation flux (25 L.h−1.m−2) during lignin diafiltration. While the lignin was exclusively condensed in the batch experiment leading to high molecular weight macromolecules (from 9 to 16 kDa), its depolymerization was effective in the bioreactor producing fragments of less than 1 kDa thanks to the in-situ extraction of the reaction products. This paper demonstrates that the reactor configuration is playing an essential role in triggering or preventing lignin condensation. It also reports the first proof-of-concept demonstrating that in-situ membrane extraction of the reactive fragments of lignin from the bulk medium can be useful against detrimental repolymerization reactions.