An expeditious microwave assisted one-pot sequential route to synthesize pyrido fused imidazo[4,5-c]quinolinesviathe Pictet-Spengler cyclization strategy has been developed. In this study, substituted 2-amino pyridines are condensed with 2-bromo-2′-nitroacetophenone to generate imidazo[1,2-a]pyridines with nitro group functionality at C-2 position. Reduction of nitro group to its amine congener in green media followed by the Pictet-Spengler cyclization strategy with substituted aldehydes led to the formation of new C-C and C-N bonds in a one-pot sequential manner. The cyclization proceeds through the CO(carbonyl)-C(H) cleavage of the aldehyde groupviaoxidative cross-coupling, transamination, cyclization and aromatization steps. Low cost reagents and a green solvent were used to facilitate the architecturally beautiful pyrido fused imidazo[4,5-c]quinoline scaffolds in high yields. The key features of this synthetic protocol are the use of microwave-assisted mild reaction conditions, one-pot sequential pathway, broad substrate scope and green media, which make it feasible for the synthesis of fused polyheterocycles. Moreover, the synthetic manipulation proceeded well with heteroaromatic and aliphatic aldehydes also in good yields. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021.