We measure the time dependence of the ratio of decay rates for the rare decay D0→K+π− to the Cabibbo-favored decay D0→K−π+. A signal of 12.7×103 D0→K+π− decays was obtained using the Collider Detector at Fermilab II detector at the Fermilab Tevatron with an integrated luminosity of 1.5 fb−1. We measure the D0−D0 mixing parameters (RD,y′,x'2), and find that the data are inconsistent with the no-mixing hypothesis with a probability equivalent to 3.8 Gaussian standard deviations.