Stroke is the leading cause of adult disability; yet, no pharmacological therapy is currently available for promoting recovery. Most patients, however, show partial recovery over time and after physical rehabilitation, revealing the brain's capacity for self-repair. But what constrains this endogenous repair from occurring sooner and to a fuller extent? Using patch-clamp electrophysiology, in cortical slices from a photothrombotic mouse model of focal stroke, we discovered that GABAergic tonic inhibition is significantly increased after stroke. This is associated with a dysfunction of the GABA transporters (GAT-3/ GAT-4) on astrocytes, suggesting that a diminished GABA clearance leads to excessive extracellular transmitter accumulation, which in turn over-activates extrasynaptic GABA(A) receptors to elevate tonic inhibition. We tested the effect of dampening tonic inhibition on motor behaviors, by chronic treatment with an alpha5-GABA(A)R-selective benzodiazepine inverse agonist (L-655,708) and found significant improvements in motor recovery. These findings indicate that excessive tonic inhibition is a critical constraint on stroke recovery, and the modulation of tonic inhibition is a promising new therapeutic approach to promote functional recovery after stroke and possibly other brain injuries.