We report the first observation of CP violation in B0+p- decays based on 152x106 U(4S)B (B) over bar decays collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We reconstruct a B0+p- CP eigenstate and identify the flavor of the accompanying B meson from its decay products. From the distribution of the time intervals between the two B meson decay points, we obtain App=+0.580.15(stat)0.07(syst) and Spp=-1.000.21(stat)0.07(syst). We rule out the CP-conserving case, App=Spp=0, at a level of 5.2 standard deviations. We also find evidence for direct CP violation with a significance at or greater than 3.2 standard deviations for any Spp value