Antimicrobial resistance has emerged as one of the foremost global public health challenges. While not a new issue, AMR has gained increasing attention due to the rise of multi-resistant pathogenic organisms, leading to higher mortality rates and significant economic burdens. To assess the knowledge, attitudes, and practices of the Bahir Dar City community regarding human and animal antimicrobial use and AMR, a community-based cross-sectional study was conducted from February to June 2023. The study area was selected purposively, and a simple random sampling approach was used to select kebeles, households, and individual participants. A total of 400 participants were enrolled in the study, with 63.25% being male and 31.25% having graduated from secondary school. Additionally, 61.5% of respondents were married, and the majority (46.5%) owned two species of animals. The findings revealed that 48.5% of the participants had moderate knowledge, 57.5% had positive attitudes, and 52.75% demonstrated good practices regarding antimicrobial resistance and usage. Chi-square analysis revealed statistically significant associations (p < 0.05) between respondents’ knowledge level and their educational level, marital status, and position in the house. Attitude level were significantly associated (p < 0.05) with educational level, marital status, occupation, house ownership, and position in the house. Practice level also showed significant association (p < 0.05) with position in the house and occupation. Furthermore, there were significant associations among knowledge, attitude, and practice: knowledge was significantly associated with attitude (χ2 = 209.91, p ≤ 0.001), knowledge with practice (χ2 = 160.43, p ≤ 0.001), and attitude with practice (χ2 = 136.95, p ≤ 0.001). In conclusion, the study found a moderate level of knowledge, positive attitude, and good practice regarding antimicrobial usage and resistance among participants. It is recommended to promote responsible antimicrobial use across all sectors and encourage interdisciplinary collaboration.