The application of sewage sludge to agricultural soil induces co-exposure of prokaryotic populations to antibiotics and heavy metals, thus exerting a selection pressure that may lead to the development of antibiotic resistance. Here, soil samples from a long-term factorial field experiment in which sewage sludge was applied to agricultural soil, at different rates (40 and 80 t ha-1) and frequencies (every 1, 2 and 4 years) of application, were studied to assess: (i) the effect of sewage sludge application on prokaryotic community composition, (ii) the links between prokaryotic community composition and antibiotic resistance profiles, and (iii) the links between antibiotic resistance and metal(oid) concentrations in amended soil. We found no significant impact of sewage sludge on prokaryotic community composition. Some antibiotic resistance genes (ARGs) correlated positively with particular prokaryotic taxa, being Gemmatimonadetes the taxon with the greatest number of positive correlations at phylum level. No positive correlation was found between prokaryotic taxa and genes encoding resistance to sulfonamides and FCA. All metal(oid)s showed positive correlations with, at least, one ARG. Metal(oid) concentrations in soil also showed positive correlations with mobile genetic element genes, particularly with the gene tnpA-07. These data provide useful information on the links between soil prokaryotic composition and resistome profiles, and between antibiotic resistance and metal(oid) concentrations, in agricultural soils amended with sewage sludge.