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Bacterial bloodstream and urinary tract infections present a huge health burden especially in low-resource settings, which is worsened by the escalating burden of antimicrobial resistance (AMR). However, surveillance data on antimicrobial susceptibility profiles of pathogens remains scarce in Malawi. Therefore, this study aimed at establishing trends and patterns of AMR among common pathogens causing adult bloodstream and urinary tract infections in Malawi. This was a secondary analysis of records from bacterial culture and susceptibility testing results of routinely collected adult blood and urinary tract samples from seven facilities in Malawi between January 2020 and August 2024. Antimicrobial susceptibility testing (AST) was performed using the disk diffusion method and interpreted according to EUCAST guidelines. The outcome of interest was the AST results of the bacterial isolates. Data were analyzed using SPSS version 28. Out of the 2787 isolates collected, 80.6% (n = 2246) were from urine samples and 19.4% (n = 541) were from blood samples. 74.1% (n = 2066) of the isolates were Gram-negative organisms. Escherichia coli (37.6%, n = 1048) and Klebsiella pneumoniae (8.3%, n = 232) were the most frequent isolates. A total of 16,696 ASTs were performed on the isolates, with 54.3% (n = 9,068) showing resistance to the antibiotics tested. Among Gram-positive organisms, there was increasing resistance to co-trimoxazole (71.4-83.3%), vancomycin (20.0-31.0%), with consistently high resistance rates to ciprofloxacin, erythromycin and gentamicin. Gram-negative organisms showed trends of increasing resistance to ceftriaxone (63.0-72.4%), co-trimoxazole (72.7-89.7%), and piperacillin and tazobactam (0.0-35.8%), with a notable significant increase in resistance to ciprofloxacin (66.7-81.0%, p = 0.001). There was an increasing trend of Enterobacteriaceae resistance to third-generation cephalosporins (58.9-71.5%). Overall, pathogens with the highest resistance include Citrobacter freundii (62.1%, n = 755/1216), Staphylococcus sp. (62.0%, n = 163/263) and K. pneumoniae (57.1%, n = 941/1648). Among the commonly isolated pathogens, E. coli, K. pneumoniae and Enterobacter spp. showed highest resistance to multiple antibiotics. The study revealed high resistance levels among pathogens that cause BSIs and UTIs in public hospitals in Malawi. Most pathogens demonstrated high resistance against multiple antibiotic classes. The high AMR trends and patterns pose a significant risk to healthcare provision, calling for enhancing surveillance and upscaling efforts to address the challenge.