In recent years, the application of probiotics to reduce lead (Pb) toxicity in organisms has gained attention. Our previous studies showed that Rhodobacter sphaeroides SC01 exhibits high Pb tolerance and efficient Pb removal from aqueous solution. In this study, the capacity and mechanisms in alleviating Pb toxicity was investigated using strain SC01 in common carp (Cyprinus carpio L.). Results showed strain SC01 successfully colonized the intestine of common carp under Pb exposure, thereby enhancing the abundance of Rhodobacter, heavy-metal-tolerant, and denitrifying bacteria, which ameliorated intestinal microenvironment and enhanced gut microbiota diversity. Strain SC01 supplementation promoted the increase in beneficial metabolites, enhanced the anti-stress capability, and facilitated damage repair in intestine. The Pb-induced alterations of gene expression in the tight junction proteins (Claudin-3c) and pro-inflammatory cytokines (IL-1β and IL-6) were obviously reversed by strain SC01. Dietary administration of strain SC01 offered direct protection against Pb-induced oxidative stress in liver, and had several beneficial effects on hematological responses and growth performance of carp. Pb accumulation in intestinal contents, intestine, liver, kidney, and blood were markedly decreased compared to the Pb group. Therefore, R. sphaeroides SC01 may be a novel dietary supplement that enhances fish growth performance and mitigates Pb-induced toxicity in aquaculture.