This study investigates the influence of boron coordination and substituent effects on the photophysical properties of two structurally related BODIPY derivatives in solution and solid state. BODIPY 1, containing an O–B–O spiro coordination motif, exhibits significantly lower fluorescence quantum yields (0.8–3.7%) and shorter excited-state lifetimes (45–450 ps) than BODIPY 2, which retains the conventional BF₂ core and displays higher fluorescence efficiencies (51–78%) and longer lifetimes (∼6 ns). Both derivatives exhibit solvent-dependent spectral shifts, suggesting the presence of excited states with partial intramolecular charge transfer (ICT) character. The Lippert–Mataga analysis suggests a slightly stronger solvent-dependent response for BODIPY 2. BODIPY 2 exhibits higher singlet oxygen generation efficiency than BODIPY 1 ( φ Δ = 0.21 vs. 0.08), which may be associated with reduced non-radiative energy dissipation pathways. In the solid state, both compounds display broadened and red-shifted emission bands consistent with intermolecular interactions and aggregation effects. Complementary fluorescence lifetime imaging microscopy (FLIM) measurements revealed differences in fluorescence lifetime heterogeneity and molecular organization between the two derivatives in the condensed phase. Overall, this comparative study improves our understanding of structure–photophysical property relationships in BODIPY systems.