Challenges with handwriting can have a negative impact on academic performance, and these challenges are commonly addressed by occupational therapy practitioners in school settings. This systematic review examined the efficacy of curriculum-based interventions to address children’s handwriting difficulties in the classroom (preschool to second grade). We reviewed and computed effect sizes for 13 studies (11 Level II, 2 Level III) identified through a comprehensive database search. The evidence shows that curriculum-based handwriting interventions resulted in small- to medium-sized improvements in legibility, a commonly reported challenge in this age group. The evidence for whether these interventions improved speed is mixed, and the evidence for whether they improved fluency is insufficient. No clear support was found for one handwriting program over another. These results suggest that curriculum-based interventions can lead to improvements in handwriting legibility, but Level I research is needed to validate the efficacy of these curricula.