Klebsiella pneumoniae (K. pneumoniae) is a high-priority antibiotic-resistant pathogen contributing significantly to the global burden of antimicrobial resistance (AMR). Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases are major resistance mechanisms commonly observed in K. pneumoniae. The present study aimed to determine the prevalence and distribution of ESBL and AmpC β-lactamase production and to evaluate associated antimicrobial resistance patterns among clinical isolates. A prospective laboratory study was conducted over one year (January-December 2020) in a tertiary care hospital, South India. Total of 100 clinical isolates of K. pneumoniae were included. Identification and antimicrobial susceptibility testing (AST) were performed using the VITEK 2 compact system, while ESBL and AmpC production were detected using standard phenotypic methods. AST demonstrated markedly high resistance rates to carbapenems (meropenem, ertapenem and imipenem), fluoroquinolones (ciprofloxacin), cephalosporins (cefuroxime, ceftriaxone, and cefepime), and β-lactamase inhibitors. Overall, 53% (n = 53) of isolates were ESBL producers, 48% (n = 48) were AmpC producers, while 24% (n = 24) exhibited co-production of both enzymes. The proportion of co-producers represents a considerable subset, suggesting a clinically relevant association with multidrug-resistance. The association between ESBL and AmpC β-lactamase production was found to be statistically not significant (P-value = 0.49). The co-existence of ESBL and AmpC enzymes was associated with a higher resistance burden across multiple antibiotic classes, underscoring its potential impact on therapeutic outcomes. These findings highlight a substantial prevalence of β-lactamase-mediated resistance and emphasize the need for continuous surveillance, implementation of robust antimicrobial stewardship programs, and proper infection control strategies to limit the spread of multidrug-resistant K. pneumoniae.