There is increasing and spread of antibacterial resistance to antibiotics worldwide. The level of knowledge and attitudes of the community regarding the use of antibiotics in Tanzania is unknown. The present study identified determinants of knowledge and attitudes regarding antibiotics use in Moshi Urban district, Northern Tanzania. A cross-sectional study was conducted from April to June 2016 among community members whereby information was collected by using questionnaires on a sample of 292 randomly selected respondents. Descriptive statistics and logistic regression analysis were used in data analysis to assess factors associated with knowledge and attitude towards antibiotic use. Out of 292 respondents, 183 (62.7%) had good knowledge regarding antibiotics use while those with adequate attitude were 255 (87.3%). Respondents with no formal education, primary and secondary education had lower odds of having good knowledge regarding antibiotics use as compared to those with higher education degree (OR=0.04, 95%CI: 0.002-0.79), (OR=0.38, 95% CI: 0.14-0.97), and (OR=0.42, 95% CI: 0.16-1.06), respectively. Respondents with good knowledge regarding antibiotics use had higher odds of having adequate attitude towards antibiotic use (OR=3.16, 95% CI: 1.49-6.70). It was concluded that knowledge and attitude regarding antibiotic use is fair. Therefore, these findings are important in strategizing targeted antibiotic awareness campaigns among population.