A complicated tectonothermal history of the Guidong Granodiorite from the Huanan Fold Belt has been revealed by using combined dating techniques. UPb single zircon and whole-rock Nd model ages suggest that the granodiorite was derived from an ancient crustal source which was probably composed of a mixture of 1.2–2.4-Ga crustal materials with a Nd model age of 1.6 Ga. The granodiorite emplacement age of 427 ± 3 Ma is defined by concordant UPb single-zircon analysis. Plagioclase, biotite, hornblende, apatite, sphene and whole rock yield an internal SmNd isochron age of 428 ± 12 Ma, consistent within the analytical errors with the UPb zircon age. Due to the presence of inherited zircon, however, the zircon data point deviates from the SmNd isochron. Four whole rocks and two mineral separates (plagioclase and hornblende) yield a RbSr isochron age of 422 ± 14 Ma, which is coincident with zircon UPb and SmNd isochron ages. Hornblende 40Ar 39Ar step-heating analysis gives a main plateau age of 371.4 ± 1.3 Ma, which is considerably younger than the crystallization age. This age is interpreted as recording a post-crystallization folding event which produced the prominent unconformity between pre-Devonian and Middle Devonian strata, and resulted in the deformation of all major minerals of the granodiorite. Since most deformed minerals have remained closed to SmNd and RbSr isotopic migration since emplacement of the granodiorite, it can be suggested that this folding event took place without significant fluid circulation and contemporaneous metamorphism. A low-temperature heating step of hornblende yields an apparent 40Ar 39Ar age of 208.5 ± 2.0 Ma which may or may not have a connection to the minimum age of the Huanan Indosinian Orogeny. A biotite 40Ar 39Ar age spectrum yields much younger apparent ages of 145 and 92 Ma which are coincident with two important Yanshanian magmatic episodes.