A design-of-experiment (DOE) parameterization was performed with the liquid sampling-atmospheric pressure glow discharge (LS-APGD) optical emission spectroscopy (OES) system to establish the optimal powering mode and operating conditions that allow for maximum signal intensity, signal-to-background (S/B) ratio, and signal-to-noise (S/N) ratio. Different from other APGD sources, the operation principles of the LS-APGD provide alternative means of applying the discharge potential. As a result of this parameterization, the sensitivity of the LS-APGD was dramatically improved, as noted by the ∼30× improvement in limit of detection (LOD), now 0.8 μg mL⁻¹ for 20 μL injections, versus earlier reports, with the solution-grounded cathode (SGC) found to be the preferred powering mode. Using the parameters from the DOE analysis, a line selection evaluation was performed for Ag, Ca, Cr, Cu, K, Mg, Na, and Zn as test elements. The best emission lines for analytical performance determination and future works were determined by measuring the stability and signal intensity for all observed lines. The chosen lines were probed for sensitivity by acquiring calibration curves for each of the analytes' transitions. When single-element solutions were used, the LODs acquired for many of the analytes were superior to previously reported LS-APGD results. While the sensitivity of the LS-APGD-OES is lower than that of an ICP-OES, the LODs for the LS-APGD are likely acceptable for those applications where portability and low-cost instrumentation are desired.