To compare gradient-boosting classifier (GBC) analysis of optical coherence tomography angiography (OCTA)-measured vessel density (VD) and OCT-measured tissue thickness to standard OCTA VD and OCT thickness parameters for classifying healthy eyes and eyes with early to moderate glaucoma. Comparison of diagnostic tools. A total of 180 healthy eyes and 193 glaucomatous eyes with OCTA and OCT imaging of the macula and optic nerve head (ONH) were studied. Four GBCs were evaluated that combined 1) all macula VD and thickness measurements (Macula GBC), 2) all ONH VD and thickness measurements (ONH GBC), 3) all VD measurements from the macula and ONH (vessel density GBC), and 4) all thickness measurements from the macula and ONH (thickness GBC). ROC curve (AUROC) analyses compared the diagnostic accuracy of GBCs to that of standard instrument-provided parameters. A fifth GBC that combined all parameters (full GBC) also was investigated. GBCs had better diagnostic accuracy than standard OCTA and OCT parameters with AUROCs ranging from 0.90 to 0.93 and 0.64 to 0.91, respectively. The full GBC (AUROC= 0.93) performed significantly better than the ONH GBC (AUROC= 0.91; P= .036) and the vessel density GBC (AUROC= 0.90; P= .010). All other GBCs performed similarly. The mean relative influence of each parameter included in the full GBC identified a combination of macular thickness and ONH VD measurements as the greatest contributors. GBCs that combine OCTA and OCT macula and ONH measurements can improve diagnostic accuracy for glaucoma detection compared to most but not all instrument provided parameters.