One feedstock of composted agro-energy co-products and agricultural residues was physically-chemically-microbiologically characterized and investigated for the phytotoxic property and the disease suppression for finding next-generation “green composts” suitable for use in horticultural soil-less systems. The suppression of three composts made of crude steam-explosion liquid-waste of miscanthus (SELWM), giant reed (SELWA) and wheat straw (SELWWS) mixed with the agro-waste mostly available in Southern Italy [CWS (SELWWS+woodchip+tomato-waste),CM (SELWM+coffee-ground+artichoke-waste) and CA (SELWA+defatted olive marc+fennel-waste)] was tested by the in vitro and in vivo experiments against seven horticultural pathosystems (Phytium ultimum/Cucumber, Phytophthora nicotianae/Tomato, Rhizoctonia solani/Bean, Sclerotinia sclerotiorum/Lettuce, Fusarium oxysporum f. sp. melonis/Melon, Fusarium oxysporum f. sp. lycopersici/Tomato,and Verticillium dahliae/Eggplant). One compost (CC) sourced from the differentiated municipal bio-waste with pathogen-specific property was employed as reference. The phytotoxicity of composts was assessed on lettuce and cress. In vitro bioassays carried out on pure colonies showed that raw compost water extracts (CWEs) were able to inhibit all of pathogens adopting a pouring technique, and that a well-cut diffusion method allowed the block of growth of the pathogens without physical interaction with compost microflora. The sterile-filtration of CWEs annulled inhibition of the pathogens, but S. sclerotiorum and V. dahliae were inhibited by sterile CWEs using a pouring procedure. In vivo tests performed under greenhouse conditions using peat-based plant growing media amended with each compost at dosage of 20% (v/v) showed multi-suppressive activity: CWS suppressed most efficiently P. ultimum, R. solani, P. nicotianae, F. oxysporum f. sp. melonis, F. oxysporum f. sp. lycopersici, V. dahliae; CM was capable to suppress P. ultimum, R. solani, P. nicotianae, S. sclerotiorum, V. dahliae; CA was suppressive against R. solani, P. nicotianae, V. dahliae. The microbiological inactivation of composts by heating treatment reduced suppression in all of pathosystems, but for S. sclerotiorum/Lettuce and V. dahliae/Eggplant the loss of suppressivity was smaller in CA, CM and CC. The predictive parameters to suppression were different: total fungal biomass for P. nicotianae; FDAH for P. ultimum; Trichoderma for R. solani; Aspergillus, Pseudomonas and Streptomyces for F. oxysporum. Instead, the parameters that drive suppression of S. sclerotiorum and V. dahliae were not well cleared. The use of composted agro-waste seems to be an efficient alternative to peat-based substrates for controlling diseases on a broad range of horticultural crops with inappreciable phytotoxic effects if added in moderate dose.