Chemical weathering is a critical Earth system process that regulates climate, ocean chemistry and the long-term carbon cycle. However, the intensity and variability of chemical weathering remain insufficiently constrained for the mid-Proterozoic (similar to 1.8-0.8 Ga), greatly limiting our understanding of the environmental context to early eukaryotic evolution. Here, we report the first coupled positive seawater Sr-87/Sr-86 (similar to 0.0007) and delta Li-7 (similar to 5 parts per thousand) isotope excursions of the Mesoproterozoic Era (1.6-1.0 Ga), which we argue signifies a substantial weathering event at similar to 1.57 Ga, characterised by increased silicate weathering rates and decreased weathering congruency. Drawing on independent geological evidence, we posit that enhanced volcanic CO2 degassing, possibly alongside accretional orogenesis, increased denudation rates and invigorated the hydrological cycle, amplifying silicate weathering and secondary clay formation. This weathering pulse broadly coincided with coeval ocean oxygenation and carbon cycle disruption, implicating it in the appearance of the earliest known decimetre-scale, multicellular eukaryotic fossils.