Sex differences have been a rarely addressed aspect in digital game-based learning (DGBL). Likewise, mixed results have been presented regarding the effects according to sex and the conditions that generate these effects. The present work studied the effects of a drill-and-practice mathematical game on primary students. The study focused on an analysis by sex, measuring motivation and learning in the practice activity. Also, two instructional mechanics were considered regarding the question answering to search for possible differences: a multiple-try feedback (MTF) condition and a single-try feedback (STF) condition. A total of 81 students from four courses and two schools participated in the intervention. The study’s main findings were as follows: (a) the girls outperformed the boys in terms of the students’ learning gains; (b) the girls presented lower levels of competence and autonomy than the boys; (c) under MTF, the girls presented lower levels of autonomy but no differences in competence contrasted with the boys; (d) under STF, the girls presented lower levels of competence but no differences in autonomy contrasted with the boys; (e) no sex differences existed in interest, effort, and value, in general, as per the instructional condition. This study enhances the knowledge of sex differences under diverse instructional settings, in particular providing insights into the possible differences by sex when varying the number of attempts provided to students.