Antibiotic resistance (ABR) is an emerging global threat to public health. Substantial evidence has indicated that community pharmacists (CPs) can play a critical role in managing the ever-increasing threat of antibiotic resistance. This study aimed to determine the knowledge, attitude, and practices of CPs (n = 180) towards antibiotics and antibiotic resistance as well as to improve the rational use of antibiotics. A two-phase mixed-methods (quantitative and qualitative) online study was conducted in Pakistan from August 2019 to March 2020 by using validated questionnaires and semi-structured interview data. Different statistical methods were used to tabulate the quantitative data, whereas inductive thematic analysis was conducted to categorize themes from the qualitative data and to draw conclusions. Approximately 64.4% of the CPs were male (mean: 29–33 years old). Overall, CPs had good knowledge of and were familiar with multidrug-resistant organisms and their roles in ABR (65.6%, median = 1, and IQR = 1), although their knowledge was poor in differentiating some antibiotic groups with their respective ABR patterns (31.1%, median = 1, and IQR = 1). Most CPs have a positive attitude towards antibiotics, with most (90.0%) identifying ABR as a critical issue in public health (median = 1 and IQR = 0). Overall, CPs’ practices towards antibiotics were somewhat acceptable, where they leaned towards educating patients about the rational use of antibiotics (52.8%, median = 1, and IQR = 1). The two main themes discovered (antibiotics and counseling of patients) were related to self-medication, while educational intervention is the main subtheme. ABR is multifactorial, with subthemes related to budget, time constraints, incompetent staff, the absence of CPs, the lack of training, and the enforcement of laws and regulations being the needs of the hour in Pakistan. Effective antibiotic stewardship programs, patient education, and awareness campaigns about antibiotics and ABR along with training of the CPs are important factors that have to be addressed in a timely manner.