While antimicrobial resistance (AMR) continues to be a major public health problem in Pakistan, data regarding trends of resistance among pathogenic bacteria remains scarce, with few studies presenting long-term trends in AMR. This study was therefore designed to analyze long-term AMR trends at a national level in Pakistan. We report here results of a comprehensive analysis of resistance, among pathogens isolated from blood and cerebrospinal fluid (CSF), between 2011 and 2015. Susceptibility data was obtained from a local laboratory with collection points all across Pakistan (Chughtai Laboratory). Resistance proportions to most commonly used antimicrobials were calculated for each pathogen over a period of five years. While Acinetobacter species demonstrated highest resistance rates to all tested antimicrobials, a sharp increase in carbapenem resistance was the most noticeable (50%-95%) between 2011–2015. Our results also highlight the presence of third and fourth generation cephalosporins resistance in Salmonella enterica serovar Typhi in Pakistan. Interestingly, where rise in AMR was being observed in some major invasive pathogens, decreasing resistance trends were observed in Staphylococcus aureus, against commonly used antimicrobials. Overall pathogens isolated from blood and CSF between 2011–2015, showed an increase in resistance towards commonly used antimicrobials.