A series of novel hybrid 6-substituted-2-chloro-3- [5-(aryl substituted)-1,3,4-oxadiazol-2-yl]quinoline 7(a-l) derivatives have been synthesized. 6-substituted-2-hydroxy-quinoline-3-carboxylic acid 3(a-d) was used as the starting material and it was made to react with aromatic acid hydrazides 6(a-c) in presence of catalytic amount of Phosphoryl Chloride (POCl3). All the newly synthesized derivatives have been characterized by Infra-Red (IR), Proton Nuclear Magnetic Resonance (1H-NMR), Carbon-13 Nuclear Magnetic Resonance (13C-NMR), mass and elemental analysis. Further, selected synthesized scaffolds were screened in vitro antimicrobial activity. The newly synthesized compounds were showed significant antibacterial activity and antifungal activity compared to standard drugs chloramphenicol and nystatin respectively.