Multi-proxy indices on annual/decadal scales during the past 600 years were developed from the surface sediments of Lake Qinghai based on 210Pb and 137Cs geochronology. The δ 13C carb, δ 18O carb, and total carbonate content are consistent with one another in trends and their variations have been mainly ascribed to regional temperature. It is suggested that the strong evaporation contributes in modifying δ 18O of lake water and δ 13C of the dissolved inorganic carbon of the surface water, and appears to be responsible for the covariance between δ 13C carb and δ 18O carb. Photosynthesis of the aquatic plants appears to have played a significant role in determining δ 15N of organic matter. The discrimination of 14N and 15N during photosynthesis may have triggered a positive linkage between temperatures and δ 15N org (after removal of the stratigraphic trend). Variations of total organic carbon (TOC), C/N ratio, and δ 13C org have been ascribed to local precipitation. TOC (after removal of the stratigraphic trend) is positively correlated with the C/N ratio ( r = 0.45, α < 0.01), and negatively correlated with δ 13C of organic matter ( δ 13C org) ( r = − 0.55, α < 0.01); while δ 13C org is negatively correlated with the C/N ratio ( r = − 0.48, α < 0.01). The climatic significance of these multi-proxy indices has been verified by comparing with the meteorological records and the climates inferred from tree rings in adjacent regions.