Purpose While many tests and indices are available to identify glaucoma progression, using them in combinations may decrease overall specificity. The aim of this study was to develop a framework for assessing glaucoma progression using structural and functional indices jointly for a fixed specificity. Methods The study included 337 eyes of 207 patients with ocular hypertension or primary open-angle glaucoma selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. All patients had at least 9 visits. Each visit had retinal nerve fiber layer thickness (RNFLT) and mean sensitivity from static automated perimetry (SAP MS) measured within a one-month window. Simple linear regression was applied to assess deterioration in each index for series of 5 to 9 visits. To identify progression using the two indices jointly, marginal significance levels set at a specificity of 95% were derived for two criteria: ANY (worsening on either RNFLT or SAP MS) and ALL (worsening on both RNFLT and SAP MS). Positive rate (percentage of eyes flagged as progressing) was determined individually for each index, as well as for the ANY and ALL criteria. Results Compared to SAP MS, RNFLT had higher positive rates (15% to 45%) for all series lengths. For the joint analyses, the positive rate was on average 12% higher for the ANY criterion compared to the ALL criterion. While RNFLT-alone had comparable positive rates and time-to-detection as the ANY criterion, each uniquely identified a subset of eyes (Kappa = 0.55 to 0.75). Conclusions This study provides a simple framework for assessing glaucoma progression with data from two tests jointly, without compromising specificity. This framework can be extended to include two or more parameters, can accommodate global or regional indices, and can eventually be used with novel parameters identified as predictive of glaucoma progression.