High-resolution analyses of the chemical and stable isotope composition of endogenic calcite from Lake Edward, an equatorial rift lake in central Africa, reveal large oscillations in African climate and moisture balance over the past 5400 yr. These oscillations indicate a series of droughts from 4900 to 400 yr B.P. that define a drought period of ∼725 yr. This period may be correlated to variations in the Indian Ocean monsoons, as documented by similar periods in sea-surface salinity records from the northern Indian Ocean. The similarities in periodicity of the Lake Edward and Indian Ocean records may indicate that low-frequency variability within the Indian and Pacific Oceans dominates millennial-scale African moisture balance and the Holocene climate of the tropical Indian Ocean.