The aims of this study were twofold: to describe associations between mentoring relationship quality (MRQ) and student academic adjustment in a formal mentoring program involving teachers as mentors and academically at-risk students as mentees, and to explore the mediating and moderating effects of student mastery goal orientation on these associations. One hundred and fifteen academically at-risk students in their first year of high school (mean age = 13.46, SD = 0.80) participated in ACCES, a one-year academic teacher-student mentoring program. Student academic adjustment and mastery goal orientation were assessed at the beginning (September) and end (June) of the program and MRQ was measured at the last mentoring meeting (May). Multiple linear regression analysis showed that teacher-student MRQ positively predicted changes in academic adjustment, particularly when at-risk students showed weak mastery goal orientation at program entry (i.e., compensatory effect). Structural equation analysis showed no mediating effect of mastery goal orientation on associations between MRQ and academic adjustment. Implications for academic mentoring practices by teachers are discussed.