Salmonella enterica serovar Indiana ( S . Indiana) has aroused widespread concern as an important zoonotic pathogen. The molecular mechanism of multidrug resistance (MDR) in S . Indiana is not known and should be assessed. We aim to investigate the molecular mechanism of MDR and the importance of large plasmids carried class 1 integrons in the MDR of foodborne S . Indiana. Class 1 integrons in 48  S . Indiana isolates and 200 isolates of 7 other Salmonella serotypes were detected by polymerase chain reaction (PCR). To analyze the antimicrobial resistance genes (ARGs) of two S . Indiana isolates, designated S . Indiana 15 and S . Indiana 222, next-generation sequencing (NGS) was performed, and the resulting sequences were compared with the complete nucleotide sequences of S . Indiana D90 and S . Indiana C629. Comparative functional analysis was conducted between the intI1 (1,014 bp) of S . Indiana 222 and the intI1 (699 bp) of S . Indiana 15. Plasmid conjugation transfer analysis was performed to analyze the horizontal gene transfer of the integrons-related resistance genes with integron-positive and integron-negative Salmonella isolates. 64.58% of S . Indiana isolates carried class 1 integrons, which was significantly higher than that of other Salmonella serotypes ( p  < 0.001). The NGS results showed that the S . Indiana 15 and S . Indiana 222 isolates carried a large plasmid with a class 1 integron and multiple ARGs, similar to S . Indiana D90 and S . Indiana C629. Two integrases found in S . Indiana isolates belong to class 1 integrases and could integrate resistance genes into specific integration sites of the integrons. The conjugation frequency of intI1 (1,014 bp) was 6.08 × 10 −5 , which was significantly higher than that of intI1 (699 bp) ( p  < 0.01). The large plasmids carrying a class 1 integron and the number of ARGs were strongly correlated ( p  < 0.001). The conjugation frequency of integron-positive S . Indiana recipient isolates was significantly higher than that of integron-negative recipient isolates ( p  < 0.05). S . Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria ( S . Enteritidis and S . Derby), which could be an important cause of the emerging pandemic of MDR clones. Graphical abstract S . Indiana containing large plasmids carrying a class 1 integron more easily captured resistance genes from other bacteria ( S . Enteritidis and S . Derby), which could be an important cause of the emerging pandemic of MDR clones.