Children's health literacy is a crucial pillar of health. This study is aimed to examine the association between health literacy and weight status among Greek schoolchildren aged 10 to 12 years old. A population-based, cross-sectional observational study enrolling 1,728 students (795 boys), aged 10 to 12 years old, was conducted during school years 2014-2016. A health literacy index (range 0-100) was created through an item response theory hybrid model, by combining a variety of beliefs and perceptions of children about health. The mean health literacy score was 70.4 (±18.7). The majority of children (63.8%) had a "high" level (i.e., >67/100) of health literacy, 30.5% had a "medium" level (i.e., 34-66/100) of health literacy, while a small proportion of children (5.7%) had a "low" level (i.e., <33/100). Girls exhibited a higher level of health literacy than boys (71.7 ± 18.3 vs. 68.8 ± 19.1, p < 0.01). Regarding body weight status, 21.7% of children was overweight and 5.0% was obese. Linear regression models showed that the health literacy score was inversely associated with children's body mass index (regression coefficient [95% CI]: -0.010 [-0.018, -0.001]), after adjusting for dietary habits, physical activity levels, and other potential confounders. Health literacy seems to be a dominant characteristic of children's weight status; therefore, school planning, as well as public health policy actions should emphasize on the ability of children's capacity to obtain, process, and understand basic health information.