Lake Biwa is the largest lake in Japan. It is a semi-closed lake surrounded by active faults, and was oxygen-rich prior to the Industrial Revolution. In this lake, arsenic concentration in core sediments was proposed as a proxy for lake-level change, due to a strong correlation between As concentration in recent sediments and water depth. Detailed elemental variations from two piston cores from water depths of 76 and 67 m were obtained from the center of the lake to examine the possible correspondence between As concentrations and paleo-environmental change during the past 40,000 years. The vertical Fe distribution pattern indicates that precipitated Fe hydroxide, the adsorbent of As ions from lake water, has been preserved in buried sediment due to oxic conditions. The change in the Ti/Al ratio suggests that the rapid drop of As content through the last several centuries is due to the increasing inflow of clayey materials generated by human activity, diluting the hydrogenous component. The As contents are fairly constant between 2000 and 9000 yr BP, and the fluctuation of equivalent water depth was 10 m at most. The increase of As content and equivalent water depth during the last two millennia should be coincident with the lake-level rise event at about 2000 yr BP, as suggested by previous investigations. However, during the last 40 kyr the extent of change of equivalent water depth is too large to explain only by tectonic movement. From about 40 cal. kyr BP to 30 cal. kyr BP, As contents significantly increased, and then gradually decreased until mid-Holocene. The change at 30 cal. kyr BP should correspond with climatic change, from wet to dry, at the marine oxygen stage 2/3 transition, with some time lag. Increases of As content are synchronized with events marked by abrupt increases in precipitation. Arsenic was dissolved in lake water as a consequence of rock and soil weathering around Lake Biwa, and then immediately precipitated with iron hydroxide into the lake sediment. Our results revealed that the historical change of As contents in core samples was influenced by the amount of As inflow to the lake from the watershed area, as well as by lake-level change. Chemical analysis of the extracts of the hydrogenous component of the samples confirmed this hypothesis.