BACKGROUND: High anisometropia is often accompanied by amblyopia. One percent atropine penalization is an important treatment for anisometropic amblyopia and is as effective as occlusion therapy. On the other hand, 1% atropine had the strongest effect on controlling refractive error and axial length (AL) changes in myopic patients. CASE PRESENTATION: A female child was diagnosed with anisometropia at the age of two. Cycloplegic retinoscopy examination revealed refraction of + 2.5 diopters the right eye and -8.5/-1.5 × 120 diopters the left eye, and full correction spectacles and patching therapy were prescribed for the child. Anisometropic amblyopia was then diagnosed because the best corrected vision acuity in highly myopic eyes is 20/100. Owing to poor compliance, visual acuity recovery in the amblyopic eye was unsatisfactory, and 1% atropine was applied two times per week for the fellow (right) eye. Since then, the fellow eye has experienced rapid myopization, with the refractive error increasing to -7.5/-1.25 × 15 diopterswithin five years. In addition, the visual acuity of the amblyopic (left) eye has improved gradually to 20/20, although the refraction status has remained stable. CONCLUSIONS: In this report, a high anisometropic amblyopia patient underwent rapid myopization in the fellow eye with constant use of 1% atropine, in contrast to the stable refraction status of the amblyopic eye.