We report the first observation of the Cabihbo-suppressed charm baryon decay ξc + → pK- π+. We observe 150 ± 22 ± 5 events for the signal. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c Σ- beam. The branching fractions of the decay relative to the Cabibbo-favored ξc + → Σ + K- π and ξ+ →c + →- ξ+ π+ π+ are measured to he B(ξc + → pK- π+)/B(ξc + → Σ- π+ K π+) = 0.22 ± 0.06 ± 0.03 and B(ξc + → ξ π+π+pK- π+)/B(ξc + →- π+ π+) = 0.20 ± 0.04 ± 0.02, respectively.