We present the first model-independent measurement of the absolute branching fraction of the Lambda_c+ -> p K- pi+ decay using a data sample of 978 fb^-1 collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The number of Lambda_c+ baryons is determined by reconstructing the recoiling D(*)- anti-p pi+ system in events of the type e+e- -> D(*)- anti-p pi+ Lambda_c+. The branching fraction is measured to be Br(Lambda_c+ -> p K- pi+) = (6.84 +- 0.24^{+0.21}_{-0.27})%, where the first and second uncertainties are statistical and systematic, respectively.