A validated, stability indicating, multiuse and sustainable HPLC-DAD method was developed for simultaneous determination and separation of the ophthalmic ternary mixture of netarsudil (NTS), latanoprost (LTP) and benzalkonium chloride (BZC) in presence of four related compounds and suspected impurities. Effectual liquid chromatographic separation was accomplished by using a Zorbax-SB Phenyl column with gradient elution of a mobile phase consisting of buffer mixture solution of phosphate and sodium pentane sulfonate (pH 3.0) and acetonitrile at flow rate 1.5 mL/min. DAD was tuned at 254 nm for measuring peak area of NTS and 210 nm for LTP and BZC. The proposed procedure showed to be effective in the stability investigation of the cited drugs. The suggested HPLC procedure was validated based on the International Council for Harmonization (ICH) guiding principles. The three analytes were determined within linearity ranges of 1–100 µg/mL, 5–200 µg/mL and 10–200 µg/mL for NTS, LTP and BZC respectively with excellent analytical performance. Assay of several ophthalmic preparations was successfully carried out using the validated method, which was further appraised together with some relevant reported methods in regard to green and white analytical chemistry aspects using AGREE and RGB-12 tools. Very few published analytical records were found for NTS/LTP mixture. After surveying the scientific literature, no documentation was retrieved for a similar inclusive stability-indicating impurity-profiling separative method for the synchronized quantitation of NTS, LTP together with co-formulated preservative BZC.