Abstract Aims Algicidal bacteria can be used for control of harmful algal bloom and extraction of algal bioproducts based on their algae-lysing activities. This work investigated the algae-lysing activity of a newly isolated algicidal bacterium, Paenibacillus polymyxa strain MEZ6 and its possible mechanisms. Methods and Results Algicidal bacteria were isolated from soil samples collected at the university campus. Co-inoculation tests identified that one isolate, MEZ6, can rapidly kill eukaryotic algae including Chlamydomonas reinhardtii, Tribonema minus, Haematococcus pluvialis, and Chlorella ellipsoidea. The strain was determined as Paenibacillus polymyxa MEZ6 based on 16S rRNA gene sequence and genome comparisons. The algicidal activity was detected in both living cells and cell-free supernatant of spent culture medium, suggesting cell-cell contact is not required for algicidal activity. Strain MEZ6 was less active towards cyanobacterial strains compared to algae. Genomic sequence and comparative proteomic analyses were performed to explore the possible algicidal mechanisms of the strain. Differentially expressed protein analysis identified a number of proteins related to polysaccharides degradation and antimicrobial secondary metabolite biosynthesis that may be involved in the algicidal activity of MEZ6. Conclusion Paenibacillus polymyxa MEZ6 is a newly discovered gram-positive algicidal bacterial strain with high lytic activity towards several algal species. Significance and Impact of the Study Our study extends the understanding of the versatile characters of Paenibacillus polymyxa and sheds new insights into its application in algae biotechnology.