The emergence of antimicrobial resistance (AMR) represents a major global threat, with antibiotic use in livestock considered a significant contributing factor. In this study, we investigated Streptococcus suis, a multidrug-resistant porcine pathogen, as a potential source of AMR gene dissemination to human-associated streptococci in Aragón, Spain. Among 91 porcine isolates collected across Spain, resistance to erythromycin and tetracycline was associated with the erm(B) and tet(O) genes, which were frequently co-located on Tn5252-family integrative and conjugative elements (ICEs) and integrative and mobilizable elements (IMEs). Tn5252-family ICEs shared 32–100% sequence identity and carried diverse combinations of AMR genes. Screening of 2,388 human clinical streptococcal isolates from different species obtained in Aragón revealed approximately 20% erythromycin resistance, particularly among S. pneumoniae and S. agalactiae. Analysis of erm(B)–tet(O) linkage in a subset of erythromycin-resistant isolates, followed by whole-genome sequencing, identified twelve isolates harboring Tn5252-family ICEs containing both resistance genes. Eight S. agalactiae isolates carried ICEs showing >95% nucleotide identity across >91% of their sequence compared with two ICEs identified in S. suis isolates recovered from the same region and time period. Conjugation assays confirmed ICE transfer from S. suis to S. agalactiae, S. pneumoniae, and S. pyogenes. In vitro experiments further demonstrated that recombination between ICEs promotes diversification of AMR gene cargo. Together, these results identify S. suis as both a reservoir and generator of ICEs carrying distinct AMR gene combinations that can be horizontally transferred to human pathogenic streptococci, leading to multidrug resistance in a single step. These findings provide strong evidence for interspecies AMR dissemination in regions with intensive pig production and underscore the need for integrated One Health strategies combining veterinary and clinical genomic surveillance with targeted interventions to limit the spread of mobile genetic elements across species.