Inoculation with beneficial microbes has been proposed as an effective practice for the improvement of plant growth and soil health. Since soil acts as a physicochemical background for soil microbial communities, we hypothesized that its management will mediate the effects of microbial inoculants on the indigenous soil microbes. We examined the effects of bacterial inoculants [Bacillus subtilis (Ba), Pseudomonas fluorescens (Ps), and both (BaPs)] on the growth of Lactuca sativa cultivated in soils that originated from an organic maize (OS) and a conventional barley (CS) management system. Moreover, the biomass and the community structure of the rhizosphere microbial communities and the soil enzyme activities were recorded. The root weight was higher in CS than OS, while the foliage length was greater in OS than CS treatments. Only in OS pots, inoculants resulted in higher biomasses of bacteria, fungi, and actinomycetes compared to the control with the highest values being recorded in Ps and BaPs treated soils. Furthermore, different inoculants resulted in different communities in terms of structure mainly in OS soils. For soil enzymes, the effect of the management system was more important due to the high organic matter existing in OS soils. We suggest that for microbial inoculation to be effective it should be considered together with the management history of the soil.