Quartz-crystal microbalance (QCM)-based gas sensors are well known for their lightweight structure, simple operation, high sensitivity, and limit of detection (LOD). The use of a QCM sensor array further enhances selectivity and enables the quantification of gas mixtures. However, the performance of QCM sensors in practical system is strongly influenced by the characteristics of measurement system, used for capturing their output frequency signals. A vector network analyzer (VNA) and a frequency counter (FC) are two common examples of such measurement systems, each offering distinct advantages and limitations. In this study, the performance of these two measurement systems is systematically investigated and compared for trace-level gas detection using QCM sensors. Herein, four different volatile organic compounds (VOCs) including isobutyric acid (IBA), trans-2-hexenal (T2H), 1-butanol (1-B), and butyl isobutyrate (BIB) were selected as analyte gases, whereas for comparison, four-channel measurement systems based on both VNA and FC were developed. These four-channel measurement systems were used to capture real-time signals from an array of four QCM gas sensors, which were coated with polyethylene glycol 1000 (PEG), 1,2,3-tris (2-cyanothoxyl propane) (TCEP), thermol-1 (THML), and polyphenyl ether (five rings) (PPE). The concentration of each analyte gas was varied to determine sensitivity and LOD for both measurement systems. A significant difference in LOD was observed for IBA with a PPE sensor. LOD was found to be 4 ppm (estimated from the relative concentration) for VNA and 30 ppm for FC. Although both measurement systems performed excellently in detecting very low concentrations of analyte gas, VNA offered a much lower LOD than FC owing to the fundamentally higher instrument resolution of VNA than of FC. Hence, we make an overall comparison between the FC- and VNA-based measurement systems for QCM gas sensing application, and the results can be considered as a key reference point for further research in this field.