Zeolitic imidazole framework-8 (ZIF-8) has been demonstrated significant potential as a support material for the fabrication of separation membranes for water treatment applications. However, the separation performance of a ZIF-8-containing membrane is limited by the poor surface and molecular sieving properties of ZIF-8. Herein, a continuous mixed-linker L-histidine@ZIF-8 (His@ZIF-8) layer was synthesized on the amyloid nanofibrils (ANFs)-modified hydrolyzed polyacrylonitrile (HPAN) membrane through a combination of self-assembly and in situ growth methods. The mixed-linker approach facilitated the tuning of surface and molecular sieving properties of ZIF-8 on the membranes, which effectively improved the overall separation and antifouling performance of the His@ZIF-8/ANFs membrane. Compared with the ZIF-8/ANFs membrane, the resultant His@ZIF-8/ANFs membrane exhibits higher water flux (42.6 vs 27.9 L/m2·h·bar) and superior heavy metal ion (Cu2+, Ni2+, Pb2+, and Cd2+) rejection (>98.6 vs 91.2%). Moreover, the His@ZIF-8/ANF membrane also exhibited a higher antibacterial efficiency of 82.9% against Escherichia coli than ANFs/HPAN membrane (16.7%). Therefore, through the mixed-linker approach, considerable modifications of the properties of ZIF-8 were realized, making it a suitable material for the preparation of membranes for wastewater treatment applications.