Myopic anisometropia (anisomyopia) is a specific type of refractive error that may cause fusion impairment, asthenopia, and aniseikonia. It is sometimes severe enough to reduce the quality of life. Several studies have investigated the treatment effects of orthokeratology (Ortho-K) and topical atropine on anisomyopia control. However, no study has compared these two interventions simultaneously until now. The cohort of this retrospective study included 124 children with anisomyopia who were treated with binocular Ortho-K lenses, 0.01% atropine, or 0.05% atropine. After a 2-year follow-up, the inter-eye difference in axial length (AL) significantly decreased in the Ortho-K group (P = 0.015) and remained stable in the two atropine groups. When comparing the myopia control effect, the use of Ortho-K lenses resulted in an obviously smaller change in AL than the use of 0.01% and 0.05% atropine (P < 0.01). Ortho-K treatment may reduce the degree of anisomyopia and stabilise the progression of myopia. Hence, Ortho-K might be a better choice for anisomyopic children.