A tandem enzyme‐catalyzed Knoevenagel reaction with acetaldehyde is presented. A new protocol for the synthesis of the desired products through a tandem process based on the enzymatic hydrolysis and Knoevenagel reaction starting from acetaldehyde precursors is disclosed. The influence of the reaction conditions including organic solvent, enzyme type, and temperature on the reaction course was tested. Further, this protocol was extended by subsequent tandem chemoenzymatic transformations leading to epoxides.