Purpose: This study analysed the relationship between caregiver-related factors (dental knowledge, attitude, behaviour, and health status) and early childhood caries. It aimed to explore better intervention methods for reducing caries prevalence in preschool children. Materials and Methods: This cross-sectional investigation was carried out in Zhejiang, China. A total of 1344 guardians (parents and grandparents) paired with their children aged 3–5 years old were enrolled. The guardians completed structured questionnaires, which included their attitude, knowledge level and oral health status. The children received dental examinations. All of the data were analysed with R software. Chi-squared and Fisher’s exact tests were used to analyse different variables. Multinomial logistic regression with stepwise procedures and curve fitting was used to explore the relationship between guardians’ risk factors and the level of early childhood caries. Results: Guardians have a great influence on the incidence of early childhood dental caries. When guardians pay attention to oral health and have a good command of relevant knowledge, then the risk of early dental caries in children is low (p = 0.027). The guardians’ dental problems, e.g. dental caries (p = 0.0002), gingival bleeding problems (p = 0.049) and chewing discomfort experience (p = 0.049), demonstrated statistically significant correlations with early childhood caries levels. Conclusion: Guardians’ attitudes, knowledge, and oral health status had a statistically significant relationship with the level of early childhood caries in their children/grandchildren. Instead of instructing schoolchildren about oral health, multiple-level dental knowledge instruction of guardians is needed to prevent early childhood caries.