Antibiotic resistance is a rising dilemma of significant implications on global public health. Few data exist for the prevalence and trends of Klebsiella pneumonia antibiotic resistance in Saudi Arabia. Therefore, we have set out to identify the prevalence and trends of Klebsiella pneumonia antibiotic resistance in King Fahad Hospital in Medina over the period between February 27, 2014, and December 31, 2018. The research was carried out as a retrospective cross-sectional study. A total of 15708 isolates taken from 1149 patients were included in the study. Statistical analysis was done using SPSS (IBM Corp, Armonk, NY). We used descriptive and trend analysis using the linear regression method. In the results, we have found unprecedented emergence of resistance to carbapenems, with 38.4% (n=436) for imipenem and 46.1% (n=371) for meropenem, which are the first choice of treatment in local guidelines, as well as high resistance rates for commonly used alternative options of treatment (40.7% (n=105) for colistin and 53.3% (n=220) for tigecycline). In addition, third and fourth generation cephalosporins showed resistance ranging from 57.5% to 77.8%. Co-resistance with imipenem was found at rates exceeding 75% for other choices of management (aminoglycosides and cephalosporins), apart from colistin and tigecycline that had rates of 53.6% (n=89) and 61.4% (n=167), respectively. In conclusion, the research showed increased resistance rates to beta-lactams, as well as an emergence of resistance to carbapenems and other alternatives of treatment like colistin and tigecycline.