We report the first observation of B±→ψ(2S)π±, a Cabibbo- and color-suppressed decay. This analysis is based on 657×106 BB̄ events collected at the Υ(4S) resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider. The measured branching fraction is (2.44±0.22±0.20)×10-5 and the charge asymmetry is A=0.022±0.085±0.016. The ratio of the branching fractions B(B±→ψ(2S)π±)/B(B±→ψ(2S)K±)=(3. 99±0.36±0.17)% is also determined. © 2008 The American Physical Society.