The determination of luminescence quantum yields by means of relative methods requires setting identical experimental conditions for both sample and reference compounds. This requirement has a critical impact on the applicability of these protocols, as it does not allow for the precise determination of low quantum-yield values using well-characterized high-quantum-yield standards. We show that using the simultaneous absorption and fluorescence-emission measurement (SAFE) approach [ Nawara and Waluk. Anal. Chem. 2017 , 89 , 8650 ], the sample and reference compounds can be effectively measured with different excitation-slit spectral bandpass or integration times, separately optimized for each chromophore. This unique feature simplifies the determination of luminescence quantum yields, allowing measurements of low quantum-yield values using well-characterized high-quantum-yield standards.