For surface-enhanced Raman scattering (SERS)-based detection, it is desirable that the SERS substrates should not only have high SERS sensitivity, but also remarkable SERS-signal reproducibility and a good affinity for the target analytes. Herein, we report large-area membranes of plasmonic Ag-nanocubes (Ag-NCs) embedded in cellulose acetate (CA) microspheres (MSs) (denoted as Ag-NCs@CA-MSs), achieved by the electrospray technique, as highly sensitive and extremely homogeneous SERS substrates with good capture ability for analyte molecules in an aqueous solution. As a result, p-aminothiophenol (a probe molecule) and methyl parathion (a toxic pesticide) with concentrations down to 10⁻⁹ M and 10⁻⁷ M could be detected, respectively. Importantly, the membranes showed remarkable SERS-signal homogeneity over a large area, with a relative signal deviation down to 2.8% in a 500 × 500 μm² area and 9.6% for the whole substrate (5 × 5 mm²). Moreover, Langmuir nonlinear fitting of the Raman intensity against the methyl parathion concentration was achieved, with a double-reciprocal plot of the Raman peak intensity versus the concentration showing a good linear relationship, making it possible for the quantitative SERS-based detection. Therefore, the Ag-NCs@CA-MS membranes showed potential for the quantitative SERS-based analysis of organic pollutants in the aqueous solution.