The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post‐transcriptional role of a MN‐specific transcriptional unit (MN2) harboring a lncRNA (lncMN2‐203) and two miRNAs (miR‐325‐3p and miR‐384‐5p) in this transition. Through the use of in vitro mESC differentiation and single‐cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2‐203 affects MN differentiation by sponging miR‐466i‐5p and upregulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR‐325‐3p and miR‐384‐5p, co‐transcribed with lncMN2‐203, act by repressing proliferation‐related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation. Synopsis: The transition from dividing progenitors to post‐mitotic motor neurons is known to be controlled by the activity of specific transcription factors. Here, the noncoding MN2 locus is identified as a bifunctional modulator of motor neuron differentiation by controlling multiple post‐transcriptional circuitries. The MN2 locus controls the transition of dividing progenitors to post‐mitotic motor neurons (MNs).MN2 function is mediated by expression of both short (miRNA) and long (lncRNA) non‐coding RNAs.The long noncoding RNA lncMN2‐203 promotes MN maturation as a sponge for miR‐466i‐5p and upregulating targets involved in MN differentiation and function.Co‐transcribed miRNAs miR‐325‐3p and miR‐384‐5p repress proliferation gene pathways through the control of cell cycle‐related factors. [ABSTRACT FROM AUTHOR]