A green, sensitive, and fast spectrofluorimetric technique for the simultaneous determination of atenolol (ATN) and losartan potassium (LSR) was developed. The proposed technique relied on the implementation of a first derivative synchronous fluorescence spectroscopy for the determination of the investigated drugs simultaneously without pretreatment procedures. The synchronous fluorescence of both drugs was measured in methanol at Δλ of 100 nm, and the first derivative peak amplitudes (1D) were measured at 321 nm for ATN and 348 nm for LSR, each at the zero‐crossing point of the other. The method was rectilinear over the concentration ranges of 100–1000 ng/mL and 50–500 ng/mL for ATN and LSR, respectively. The proposed technique was successfully applied for the determination of the studied drugs in their laboratory‐prepared mixture and pharmaceutical formulations, demonstrating high mean recoveries of 100.54% for ATN and 100.62% for LSR, without interference from common excipients. The results were in good agreement with those obtained by the comparison method. Three recent greenness assessment tools, the Eco‐Scale tool, the Green Analytical Procedure Index (GAPI) metric, and the Analytical GREEnness metric approach, were employed to affirm the greenness of the proposed method. The developed method was proven to be eco‐friendly.