In order to observe the occurrence of fusarium wilt in watermelon plants after colonization for 40 days in 5–year watermelon continuous cropping soil with and without calcium oxide, 16S rDNA sequencing was carried out on the soil by Illumina Hiseq high–throughput assay and the bacterial population characteristics of rhizosphere soils with and without calcium oxide were compared. The results showed that in continuous cropping soil without calcium oxide, the incidence of Fusarium wilt in watermelon was 87.5%, while the incidence of fusarium wilt in continuous cropping soil with calcium oxide was 35.4%, and the relative control effect of watermelon wilt was 59.5%. The bacterial diversity index and bacterial richness of continuous cropping soil with calcium oxide were higher than those of continuous cropping soil without calcium oxide. The dominant flora of soil was changed by continuous cropping with calcium oxide application. Among the top 30 soil bacteria with relative high abundance at the generic level, Mizugakiibacter, Crenotalea, Rhodanobacter, Acinetobacter, Dyella and Bryobacter showed significant positive correlations whereas Flavisolibacter, sphingomonas, Gemmatimonas, Opitutus and Devosia showed significant negative correlations with fusarium wilt disease incidence.