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Background: Many studies reported the effects of antibiotic exposure on E. coli bacterial growth and cell modification. However, scarce descriptive information on ultrastructural effects upon exposure of commercial antibiotics. Methods: This study described the morphological and ultrastructural alterations caused by selected antibiotics (amoxicillin-clavulanate, ceftriaxone, polymyxin B, colistin, gentamicin, and amikacin) that targeted cell wall, plasma membrane, and cytoplasmic density, and also proteins synthesis. We determined extracellular morphological changes of exposure through scanning electron microscopy (FESEM) and intracellular activities through transmission electron microscopy (TEM) investigation. Results: FESEM and TEM micrograph of E. coli exposed with selected antibiotics shows ultrastructural changes in beta-lactam class (amoxicillin-clavulanate, ceftriaxone) elongated the cells as the cell wall was altered as it inhibits bacterial cell wall synthesis, polymyxin class (polymyxin B, colistin) had plasmid and curli-fimbriae as it breaking down the plasma/cytoplasmic membrane, and aminoglycoside class (gentamicin, and amikacin) reduced ribosome concentration as it inhibits bacterial protein synthesis by binding to 30 s ribosomes. Conclusion: Morphological and ultrastructural alterations of E. coli’s mechanism of actions were translated and depicted. This study could be reference for characterization studies for morphological and ultrastructural of E. coli upon exposure to antimicrobial agents.