(1) Background: Antibiotic resistance (ABR) has been escalating to seriously high levels worldwide, accelerated by the misuse and overuse of antibiotics, especially in Vietnam. In this work, we investigated the Vietnamese public socio-demographic and knowledge factors associated with inappropriate practices of antibiotics to better understand the country’s antibiotic use and ABR. (2) Methods: To this end, a cross-sectional survey was conducted among Vietnamese people aged 18–60 years via Computer Assisted Telephone Interviews (CATIs) from May 2019 to November 2019. (3) Results: Among 3069 responses distributed equally in all 63 provinces in Vietnam, 1306 respondents completed the survey (response rate of 42.5%). Socio-demographically, most participants were male (56.4%), 18–25 years old (40.4%), located in Southern Vietnam (67.1%), highly educated (93.7%), and possessed medical insurance (95.3%). Respondents with higher education levels (college and above) had 2.663 times higher knowledge scores than those with lower education levels (p < 0.001). High-income respondents possessed more knowledge than low-income respondents (OR = 1.555, CI 95% 0.835–2.910, p = 0.024). Students, non-skilled workers, skilled workers, and professionals and managers had 0.052, 0.150, 0.732, and 0.393 times lower practice scores than the unemployed group, respectively (p < 0.001). Furthermore, respondents with higher/adequate knowledge scores had higher practice scores than those with inadequate knowledge scores (p < 0.05). (4) Conclusions: The findings indicate that socio-demographic differences in knowledge and practices exist, and focusing on these issues should be the priority in forthcoming interventions. The research data also provide information for policy makers to raise the community’s awareness of ABR.