Attainment of optimal health calls for collaboration between animals, humans, and environmental health professionals together with understanding the consequences of animals, humans, and environment interactions on health. In cognizant of this, the government in Tanzania introduced One Health Strategic Plan (2015–2020), little is empirically known on how this plan has facilitated the enhancement of knowledge, awareness, attitudes, and practices (KAPs) under One Health Approach (OHA). This article analyses KAPs under OHA from a cross-sectional study conducted in Morogoro, Tanzania. Data were collected by a questionnaire from 1440 respondents obtained through a multistage sampling procedure, 80 Focus Group discussions (FGDs) participants and 16 key informant interviewees. IBM-SPSS v.20 analysed quantitative data while qualitative data were organised into themes on specific objectives. Results revealed that only 32.3% (95% CI:30.3 to 35.3) had adequate OH knowledge. Only 5% (95% CI:4.0 to 6.1) were aware of OHA concept and practices; 3.8% (CI 95%, 2.8 to 4.8) managed to identify collaborative efforts and strategies, and 2.5% (CI 95%, 1.7 to 3.4) correctly explained/ described OHA. Whereas, 38.5% (95% CI:32.6 to 37.5) had a positive (favourable) attitude towards OHA. Despite the efforts outlined in the OH Strategic Plan to promote OHA, there is little awareness and knowledge on OHA. This indicates that the One Health Strategic Plan (2015–2020) and other initiatives have not significantly facilitated the enhancement of KAPs. This study recommends strengthening efforts towards OHA information dissemination to enhance awareness and knowledge on the concept and practices.