Tuberculosis remains one of the major causes of morbidity and mortality in Equatorial Guinea, with an estimated incidence of 280 per 100,000 inhabitants, an estimated mortality rate of 96 per 100,000 inhabitants, and a treatment non-adherence rate of 21.4%. This study aimed to identify the factors associated to TB-related knowledge, attitudes, and stigma in order to design community intervention strategies that could improve TB diagnostic and treatment adherence in Equatorial Guinea. A nationwide cross-sectional survey of 770 household caregivers was conducted in Equatorial Guinea about TB knowledge, attitudes, and practices. Knowledge, attitude, and stigma scores were calculated through correct answers and the median was used as cut-off. Associated factors were analyzed calculating prevalence ratio (PR) and a 95% confidence interval (95% CI) through Poisson regression with robust variance. The percentage of women was 53.0% and median age was 46 years (IQR: 33–60). The percentage of caregivers with high TB related knowledge was 34.9%, with a bad attitude (52.5%) and low stigma (40.4%). A greater probability of having good knowledge was observed in those 45 years old or less (PR: 1.3, 95% CI: 1.1–1.6), those with higher education level (PR: 1.4, 95% CI: 1.1–1.8) and higher wealth (PR: 1.4, 95% CI: 1.0–2.0), while sex (PR = 0.8, 95% CI: 0.6–0.9), religion (PR = 1.4, 95% CI: 1.0–1.8), and good knowledge (PR = 1.4, 95% CI: 1.2–1.7) were associated with good attitudes. Wage employment (PR = 95% CI: 1.2–1.4), feeling well informed (PR = 0.7, 95% CI: 0.6–0.8), having good TB knowledge (PR = 1.3, 95% CI: 1.1–1.7), and some sources of information were associated with having lower TB-related stigma. This study found that a high percentage of caregivers in Equatorial Guinea lack important knowledge about TB disease and have bad attitudes and high TB-related stigma. Given the epidemiological situation of TB in the country, it is urgent to improve TB knowledge and awareness among Equatorial Guinea’s general population.