As a new mode of public transportation, self-driving buses offer numerous benefits, including increased traffic safety, reduced energy consumption, optimized road-resource ratios, and improved traffic accessibility. However, there is still a need to fully understand the public’s perception of self-driving buses before they are widely used. As a result, we investigated whether individual differences (including demographic and personality traits) influence the acceptance of self-driving buses in Nanjing, China. A questionnaire was given to 453 people in Nanjing, and the sample data were analyzed using a one-way analysis of variance (ANOVA). According to the findings, gender, age, educational background, income level, frequency of use, and personality traits all had a significant impact on the acceptance of self-driving buses. This study’s findings provide empirical data to help guide future research on self-driving buses, as well as a theoretical foundation for self-driving-bus development and design.