Introduction: To evaluate the association of focal lamina cribrosa (LC) defect with asymmetric visual field (VF) loss in normal-tension glaucoma (NTG) through intereye comparisons. Methods: Paired eyes were divided into better and worse eyes according to the mean deviation (MD), and ocular parameters were compared between them. Furthermore, patients in the asymmetric group were classified as subgroup A (one eye with LC defect and the fellow one without), subgroup B (both eyes without LC defect), and subgroup C (both eyes with LC defect). Generalized estimation equation approach was used to evaluate the association between ocular parameters and asymmetric VF. Results: A total of 140 eyes of 70 NTG patients were included in the asymmetric group. LC defects were more common in better eyes than that in worse eyes (27/70 [38.57%] vs. 10/70 [14.29%], p = 0.001), and all eyes with LC defect had myopia. Multivariate analysis revealed that the presence of LC defect was significantly associated with better eyes in the asymmetric group (odds ratio, 0.27; p = 0.001). For subgroup A, eyes with LC defects exhibited lower peak IOP (p = 0.011) and lower mean IOP (p = 0.018) than the fellow eyes without. In addition, longer AL (p = 0.025) and larger tilt ratio (p = 0.032) were found in eyes with LC defects. For subgroup B without LC defects, larger tilt ratio was shown to be a risk factor for VF loss (odds ratio, 6.13; p = 0.001). There was no significant difference of binocular parameters except for MD (p < 0.001) in subgroup C. Conclusions: LC defects in myopia were suggested to be associated with better eyes in NTG with asymmetric VF loss. However, in patients without LC defect, larger tilt ratio was a risk factor for VF defect. There might be different pathological mechanisms in asymmetric VF loss for different NTG subtypes.