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Colistin is an important last-line antibiotic to treat highly resistant <i>Enterobacter</i> infections. Resistance to colistin has emerged among clinical isolates but has been associated with a significant growth defect. Here, we describe a clinical <i>Enterobacter</i> isolate with a deletion of <i>mgrB</i>, a regulator of colistin resistance, leading to high-level resistance in the absence of a growth defect. The identification of a path to resistance unrestrained by growth defects suggests colistin resistance could become more common in <i>Enterobacter</i>.