Infectious disease is one of the greatest causes of morbidity and mortality worldwide, and with the emergence of antimicrobial resistance, the situation is worsening. In order to prevent this crisis, antimicrobial resistance needs to be monitored carefully to control the spread of multidrug-resistant bacteria. Therefore, in this study, we aimed to determine the prevalence of infection caused by Klebsiella pneumoniae and investigate the antimicrobial profile pattern of K. pneumoniae in the last eleven years. This retrospective study was conducted in a tertiary hospital in Makkah, Saudi Arabia. Data were collected from January 2011 to December 2021. From 2011 to 2021, a total of 61027 bacterial isolates were collected from clinical samples, among which 14.7% (n = 9014) were K. pneumoniae. The antibiotic susceptibility pattern of K. pneumoniae revealed a significant increase in the resistance rate in most tested antibiotics during the study period. A marked jump in the resistance rate was seen in amoxicillin/clavulanate and piperacillin/tazobactam, from 33.6% and 13.6% in 2011 to 71.4% and 84.9% in 2021, respectively. Ceftazidime, cefotaxime, and cefepime resistance rates increased from 29.9%, 26.2%, and 53.9%, respectively, in 2011 to become 84.9%, 85.1%, and 85.8% in 2021. Moreover, a significant increase in the resistance rate was seen in both imipenem and amikacin, with an average resistance rate rise from 6.6% for imipenem and 11.9% for amikacin in 2011 to 59.9% and 62.2% in 2021, respectively. The present study showed that the prevalence and drug resistance of K. pneumoniae increased over the study period. Thus, preventing hospital-acquired infection and the reasonable use of antibiotics must be implemented to control and reduce antimicrobial resistance.