Infants with nontyphoidal Salmonella (NTS) enterocolitis should be treated with antibiotics. However, it is unclear if newborns have a problem with antimicrobial resistance (AMR). This research aimed to better understand the nature of NTS infections in newborns. Less-than-3-month-old infants with NTS infections were enrolled and split into 2 groups, or “cohorts” (diagnosed 2010–2015 or 2016–2021). Invasive nontuberculous Salmonella (iNTS) was classified as Salmonella found in blood or cerebrospinal fluid. Clinical characteristics, antimicrobial resistance, and serogroups were compared among groups. Around 102 newborns were infected with NTS bacteria, 6.9% of which were iNTS. Infants with iNTS infections tended to be younger, spend more time in the hospital, and take longer courses of antibiotics. There were more than twice as many cases of iNTS in people resistant to ciprofloxacin as in people who were not. Salmonella serogroups C2 and E were the most common ones to exhibit iNTS. In the last decade, the most prevalent serogroups have been B (44%), E (26%), and C2 (16%). NTS was associated with a dramatic rise in AMR to ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and more than or equivalent to 3 antibiotics. The prevalence of both widespread drug resistance and multidrug resistance in NTS rose dramatically as well. Serogroups changed throughout time, with groups C2 and E emerging as major contributors to iNTS in recent years. It’s important to note that iNTS AMR is particularly on the rise. Infants with NTS infections between the ages of 1 and 3 months old should rethink receiving regular antibiotic treatment in light of the low iNTS rate and significant AMR. For therapy solutions to be developed, more extensive research is needed.