Numerous factors are proposed to affect high school students’ academic achievement; however, these factors may not reveal all possible causal relationships. This study conducted path analysis to examine the direct and indirect effects of interpersonal relationships, life satisfaction, self-esteem, anxiety, and depression on the academic achievement of senior high school students. Two hundred and eighty-five students from five schools in Chiang Mai, Thailand, aged 14–19 years, were included for data analysis. The fit indices of all models were in agreement with the empirical data. Anxiety levels had a significantly positive direct effect on achievement, whereas depression had a negative direct effect on achievement. Additionally, self-esteem, life satisfaction, and interpersonal relationships had negative indirect effects on depression and anxiety. A program that stimulates the optimal and appropriate level of anxiety may be useful. An appropriate level of anxiety appeared positively related to academic achievement, but a high level of anxiety relatively influenced the incidence of depression. Thus, encouraging self-esteem, interpersonal relationships, and life satisfaction can promote academic ability and decrease the risk of depression. Further well-designed and large sample-size studies should be conducted to confirm these findings. The interplay of all studied factors may account for the variation in academic achievement, depression, and anxiety of 11.60%, 42.80%, and 17.60%, respectively.