The Guaymas Basin, Gulf of California, is an important site for paleoclimate study due to ideal preservation conditions and high sedimentation rates, which allow for high-resolution analysis of paleoclimate records and investigation of climatic and oceanographic processes that operate over timescales not resolved by modern instrumental records. Furthermore, the Guaymas Basin receives some water advected at depth from the Eastern Tropical North Pacific (ETNP), a region where oceanographic processes are closely coupled to the global climate system. The past climate and oceanography of the Gulf of California and ETNP have been well studied at low resolution over glacial-interglacial timescales: the goal of this study is to elucidate Mid- to Late Holocene oceanographic and climate changes at a higher resolution than previous studies in order to resolve decadal to centennial variance. Three main conclusions can be drawn from the new high-resolution records presented here. First, a careful comparison of radiocarbon dating and layer counting data calls into question the completeness of varved marine sequences in the Guaymas Basinches Second, stable isotopes, elemental composition data, XRF core scan trace metal counts, and smear slide analysis are used to identify a significant change in mean conditions and ecosystem structure at ~2800 yr BP, which is probably driven by southward displacement of the Inter-tropical Convergence Zone (ITCZ). Notably, mean bulk delta15N is ~0.6‰ lower after 2800 yr BP, suggesting decreased denitrification and improved ventilation. Third, important frequencies of variance at centennial and decadal periodicities are identified. Comparison of these new high-resolution proxy records to previous work in other regions suggests that Mid- to Late Holocene changes in the Guaymas Basin may be linked to climate changes across a larger spatial scale.