Three new pyridine-carbonitrile derivatives, namely, 6-(5-chlorothiophen-3-yl)-2-methyl-4-p-tolylpyridine-3-carbonitrile (1), 6-(5-chlorothiophen-3-yl)-4-(4-fluorophenyl)-2-methylpyridine-3-carbonitrile (2), and 6-(5-chlorothiophen-3-yl)-2-methyl-4-(naphthalen-4-yl)pyridine-3-carbonitrile (3), have been synthesized. The compounds were characterized using IR, 1H and 13C NMR, and HRMAS. The structures were confirmed by X-ray structural analysis for all three derivatives. The molecular structure consists of the central pyridine ring bearing four substituents: a monochlorothiophene ring, a methyl group, a carbonitrile group and an aryl group. The crystal structure is dominated by aryl-aryl offset-face-to-face π···π stacking interactions. In addition, C—H···Cl [in (1)], C—H···N/F [in (2)], and C—H···N [in (3)] interactions are found as shape-complementary motifs. All interactions consolidate crystal supramolecularity. Photophysical measurements show fluorescence properties for derivatives (1)–(3). The derivatives were found to possess a blue emission in the range of λ = 366–390 nm. These findings can be useful for designing new compounds with improved properties for various applications, including optoelectronics, materials science, and chemical sensing.