Objective To assess the prevalence of β-lactam resistance among nontyphoidal Salmonella (NTS) isolates including ampcillin and third-generation cephalosporins, detect the production of ESBL and analyzing their molecular mechanisms, and to provide data basis for relevant diseases control and treatment. Methods NTS isolates were collected from patients, food and river water in Ningbo from 2005 to 2016 and were tested for resistance to ampicillin, cefotaxime and cefotaxime/clavulanate using the disc diffusion method specified in Clinical and Laboratory Standards Institute (CLSI). Among isolates resistant to β-lactam anbiotics, β-lactamase genes (blaCTX-M, blaTEM, and blaOXA) and two types of integrons, class 1 and class 2, were amplified. Results Overall, 893 NTS isolates were obtained from patients, food and river water with resistance rates to ampicillin and cefotaxime, and ESBL-production rate of 37.8%(338/893), 7.7%(69/893)and 7.3%(65/893), respectively. The top three β-lactam-resistant serotypes were Salmonella indiana (100.0%,11/11), Salmonella derby (69.7%,23/33) and Salmonella typhimurium (57.4%,148/258). Other serotypes that were tested positive for cefotaxime resistance and ESBL production were Salmonella agona (4 isolates), Salmonella kentucky (2 isolates) and Salmonella muenster (2 isolates). Ampicillin-resistant isolates mainly contained blaTEM gene. Cefotaxime-resistant isolates often contained blaCTX-M and blaOXA gene. Most β-lactam-resistant isolates were found to have class 1 integron with complete structure. Conclusion High prevalence of ampicillin resistance and moderate prevalence of third-generation cephalosporins resistance existed in NTS isolates from patients, food and river water. High level of β-lactam resistance was found in several NTS serotypes such as Salmonella indiana, Salmonella derby and Salmonella typhimurium. Complicated molecular mechanisms existed in β-lactam-resistant NTS isolates, which might pose great risk to the spread of antibiotic resistance. Strengthened surveillance on β-lactam resistance and exploration of relevant molecular mechanisms were required.