Lesotho has one of the highest rates of tuberculosis (TB) incidence and TB-HIV co-infection in the world. Our study aimed to assess the knowledge, attitude and associated factors towards TB in the general population of Lesotho. A cross-sectional analysis from the Lesotho Demographic and Health Survey (LDHS) 2014 was carried out among 9247 respondents. We used the chi-square test as well as univariate and multivariate logistic regression analyses to assess the associations of socio-demographic variables with respondent knowledge of and attitude towards TB. The overall knowledge of TB in the general population of Lesotho was adequate (59.9%). There was a significant difference between female and male respondents regarding knowledge about TB (67.0% vs. 41.8%). Almost 95% of respondents had “heard of an illness called tuberculosis”, and 80.5% knew that TB can be cured. Only 11.5% knew the correct cause of TB (TB is caused by Mycobacterium tuberculosis). Female respondents were relatively aware of TB, knew about the correct cause and mode for transmission of TB and knew that TB is a curable disease compared to male respondents. A higher proportion of respondents (72.8%) had a positive attitude towards TB. Multivariate logistic regression analysis showed that sex (adjusted odds ratio [AOR] = 2.45, 95% CI: 2.10–2.86; p < 0.001), age (AOR) =1.76, 95% CI: 1.29–2.41; p < 0.001), educational level (AOR = 6.26, 95% CI: 3.90–10.06; p < 0.001), formerly married or cohabitated (AOR = 1.42, 95% CI: 1.10–1.85; p = 0.008), mass media exposure (AOR = 1.33, 95% CI: 1.08–1.64; p = 0.008) and occupation (AOR = 1.20, 95% CI: 1.00–1.44; p = 0.049) were strongly associated with respondent knowledge of TB. Sex (AOR = 1.19, 95% CI: 1.01–1.41; p = 0.034), educational level (AOR = 1.661, 95% CI: 06–2.60; p = 0.028), mass media exposure (AOR = 1.31, 95% CI: 1.06–1.62; p = 0.012) and occupation (AOR = 1.26, 95% CI: 1.04–1.52; p = 0.016) were strongly associated with respondent attitude towards TB. Strategies to improve the knowledge of Lesotho’s people about TB should focus on males, young residents, those who are illiterate, those who are unmarried and farmers. Special attention should be given to males, young residents, rural residents, those who are illiterate and farmers to improve their attitude towards TB in Lesotho.