Although synthetic pesticides play a major role in plant protection, their application needs to be reduced because of their negative impact on the environment. This applies also to copper preparations, which are used in organic farming. For this reason, alternatives with less impact on the environment are urgently needed. In this context, we evaluated eight isolates of the genus Lysobacter (mainly Lysobacter enzymogenes) for their activity against plant pathogens. In vitro, the investigated Lysobacter isolates showed broad antagonistic activity against several phytopathogenic fungi, oomycetes and bacteria. Enzyme assays revealed diverse activities for the tested isolates. The most promising L. enzymogenes isolate (LEC) was used for further detailed analyses of its efficacy and effective working concentrations. The experiments included in vitro spore and sporangia germination tests and leaf disc assays as well as ad planta growth chamber trials against Alternaria solani and Phytophthora infestans on tomato plants, Pseudoperonospora cubensis on cucumbers and Venturia inaequalis on young potted apple trees. When applied on leaves, dilutions of a culture suspension of LEC had a concentration-dependent, protective effect against the tested pathogens. In all pathosystems tested, the effective concentrations were in the range of 2.5–5% and similarly efficacious to common plant protection agents containing copper hydroxide, wettable sulphur or fenhexamid. Thus, the isolate of L. enzymogenes identified in this study exhibits a broad activity against common plant pathogens and is therefore a promising candidate for the development of a microbial biocontrol agent.