Muscle atrophy is associated with negative outcomes in a variety of diseases. Identification of a common therapeutic target would address a significant unmet clinical need. Here, we identify a long non-coding RNA (lncRNA) (muscle-atrophy-associated transcript, lncMAAT) as a common regulator of skeletal muscle atrophy. lncMAAT is downregulated in multiple types of muscle-atrophy models both in vivo (denervation, Angiotensin II [AngII], fasting, immobilization, and aging-induced muscle atrophy) and in vitro (AngII, H2O2, and tumor necrosis factor alpha [TNF-α]-induced muscle atrophy). Gain- and loss-of-function analysis both in vitro and in vivo reveals that downregulation of lncMAAT is sufficient to induce muscle atrophy, while overexpression of lncMAAT can ameliorate multiple types of muscle atrophy. Mechanistically, lncMAAT negatively regulates the transcription of miR-29b through SOX6 by a trans-regulatory module and increases the expression of the neighboring gene Mbnl1 by a cis-regulatory module. Therefore, overexpression of lncMAAT may represent a promising therapy for muscle atrophy induced by different stimuli. Xiao and colleagues report that lncMAAT is a common regulator of muscle atrophy. Inhibition of lncMAAT is sufficient to induce muscle atrophy by cis- and trans-regulatory actions. Overexpression of lncMAAT can ameliorate multiple types of muscle atrophy. Their work provides a promising therapy for muscle atrophy induced by different stimuli.