Microbial fuel cell (MFC) technology has been developed for wastewater treatment in the anodic chamber, and heavy metal reduction in the cathodic chamber. However, the limited extracellular electron transfer (EET) rate of exoelectrogens remained a constraint for practical applications of MFCs. Here, a MFC system that used the electricity derived from anodic wastewater treatment to drive cathodic Cr6+ reduction was developed, which enabled an energy self-sustained approach to efficiently address Cr6+ contamination. This MFC system was achieved by screening exoelectrogens with a superior EET rate, promoting the exoelectrogenic EET rate, and constructing a conductive bio-anode. Firstly, Shewanella algae-L3 was screened from brewing wastewater acclimatized sludge, which generated power density of 566.83 mW m−2. Secondly, to facilitate EET rate, flavin synthesis gene operon ribADEHC was overexpressed in engineered S. algae-L3F to increase flavins biosynthesis, which promoted the power density to 1233.21 mW m−2. Thirdly, to facilitate interface electron transfer, carbon nanotube (CNT) was employed to construct a S. algae-L3F-CNT bio-anode, which further enhanced power density to 3112.98 mW m−2. Lastly, S. algae-L3F-CNT bio-anode was used to harvest electrical energy from brewing wastewater to drive cathodic Cr6+ reduction in MFC, realizing 71.43% anodic COD removal and 98.14% cathodic Cr6+ reduction. This study demonstrated that enhanced exoelectrogenic EET could facilitate cathodic Cr6+ reduction in MFC.