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PURPOSE To determine if the three-dimensional eyeball shape is associated with the positions of the central retinal vascular trunk (CRVT) and the externally oblique border (EOB) in the optic nerve head (ONH). DESIGN Prospective cross-sectional study PARTICIPANTS: Fifty-six (56) subjects (112 eyes) with a diagnosis of glaucoma or glaucoma suspect METHODS: The three-dimensional shape of the eyeball on 3D-MRI scans was classified according to the dimension of the longest diameter: axial dimension (prolate sphere), group 1; horizontal dimension (horizontally oblate sphere), group 2; and vertical dimension (vertically oblate sphere), group 3. The deviation of the CRVT, as a surrogate of lamina cribrosa (LC) shift, was measured from the center of the Bruch's membrane opening (BMO) demarcated by OCT imaging, with the horizontal midline as 0° and the superior location as a positive value. The angular location of the longest EOB was also measured. MAIN OUTCOME MEASURE Positions of CRVT and EOB according to the three-dimensional shape of an eyeball RESULTS: Among 112 eyes, 54 (48%) had a prolate shape (group 1), 23 (21%) a horizontally oblate shape (group 2), and 35 (31%) a vertically oblate shape (group 3). The angular deviation of the CRVT differed among the groups: to the nasal side in group 1, to the temporal side in group 2, and along the vertical meridian in group 3. In cases of asymmetric eyeball shape, the CRVT was deviated toward the undergrown side from the overgrown side, regardless of grouping. The angular location of the longest EOB was in the direction opposite to the CRVT position (P < 0.001). A generalized estimating equation analysis revealed that the temporal location of the CRVT was associated with older age (P = 0.001), nasal location of the longest EOB (P < 0.001), and oblate shape of the eyeball (P <0.001, group 2; P = 0.007, group 3). CONCLUSIONS The position of the CRVT and EOB were associated with the three-dimensional eyeball shape. Considering that infant ONH morphology is highly uniform, various modes of eyeball expansion during growth can result in diverse directionalities of offset between the LC and BMO in adults.