The inner walls of a glass microreactor were functionalized in a one-step procedure with a single layer of a strong perfluoroalkylsulfonic acid. The applicability of the catalytic device was demonstrated in the successful hydrolysis of benzaldehyde dimethyl acetal in acetonitrile, achieving quantitative conversion within a residence time of only 60 s. Furthermore, the catalytic system showed high conversion for the Friedlander quinoline synthesis between 2-aminobenzophenone and ethyl acetoacetate. The cyclization of pseudoionone in methylcyclohexane proved the wide applicability of the acid-functionalized microreactor also for reactions carried out in apolar media. The platform showed activity for 6 h to 2 days, depending on the solvent, and was reactivated by simple treatment with the catalyst precursor.