In 2003, the government of Tanzania introduced the accredited drug dispensing outlet (ADDO) program to improve access to good-quality medicines in rural and peri-urban areas that have frequent drug shortages in public health facilities and few or no registered pharmacies. However, increasing access may also contribute to antimicrobial resistance (AMR) due to the potential overuse and misuse of drugs. We conducted a cross-sectional household survey in four regions in mainland Tanzania to characterize consumer care-seeking habits and medicines use and to determine the extent to which members of the community are knowledgeable about antimicrobials and AMR. We revealed that communities in the four regions have low levels of knowledge of the concepts of antimicrobials and their use and AMR. Level of public understanding rose with wealth status and education. Only one-third of 1,200 respondents (33.6%) had ever heard of a medicine called an antimicrobial, and 5–15% could name at least one antimicrobial spontaneously. Some thought other medicines, such as paracetamol, were antimicrobial (7.5%). People were equally likely to agree that pneumonia should be treated with an antimicrobial (21.4%) as well as common cold (28.4%). Understanding of AMR risks was better, particularly related to HIV and AIDS (32.2%) and malaria (38.6%)—most likely due to information campaigns focused on those two diseases. The level of knowledge decreased the further away respondents lived from an ADDO and where ADDO density was lower, which supports the use of ADDO dispensers as sources of community information and change agents for more appropriate medicine use. Lack of knowledge about antimicrobials and AMR in Tanzanian communities needs to be addressed through multi-pronged strategies that focus on prescribers and the public— especially those who are poorer and less educated.