The early Paleozoic witnessed two spectacular radiations of marine organisms—the Cambrian (Є) Explosion and the Great Ordovician (O) Biodiversification Event. However, the period between them was characterized by a marine biodiversity plateau attributed to recurring biocrises. In the current study, we present the I/Ca records from slope lime mudstones of the Green Point Formation in western Newfoundland, along with a three-sink U-isotope mass balance model and previously reported limestone δ238Ucarb signals of the same interval, to further explore oceanic redox conditions at the Є-O boundary. The I/Ca ratios of the lime mudstones, deposited along the eastern Laurentian (western Iapetan) continental slope, exhibit a narrow range between 0.02 and 0.33 μmol/mol. Poor correlations between the I/Ca values and their [Sr], δ18O, Mn/Sr, Fe/Sr, Mg/Ca, and δ13Corg counterparts, together with near-micritic textures of the limestones, argue against significant influences of postdepositional alterations on the I/Ca signatures. The iodine-depleted lime mudstones, with I/Ca values well below the Proterozoic Eon baseline I/Ca ratios (∼0.5–1 μmol/mol), suggest the presence of shallow marine oxic-anoxic interfaces along the regional continental margin. Substantially low limestone I/Ca ratios (<0.5 μmol/mol) and dysoxic to anoxic depositional conditions have also been reported from several other age-equivalent sections deposited along the shelf and slope of ancient Iapetan and Laurentian continental margins. As a result, seawaters surrounding the Iapetan and Laurentian continental margins at the Є-O transition might have been commonly poorly oxygenated with shallow oxyclines or expanded oxygen minimum zones in the shelf and/or slope areas. This interpretation is further supported by our three-sink U-isotopemass balance modeling, which predicts widespread marine anoxia at the Є-O boundary with anoxic to euxinic water covering 1.0–21.1% of the ocean floor, significantly higher than the modern day (∼0.2%). Furthermore, the wide range of the oceanic δ238UOC (−1.22 to −0.25‰) values, estimated from the limestone δ238Ucarb signals, might reflect oceanic redox oscillations during this period. However, the δ238UOC fluctuations could also be attributed to variable accumulations of the 238U-enriched authigenic U phases during early diagenesis. Overall, evidence from the lime mudstone I/Ca ratios and the estimated extent of marine anoxia at the Є-O boundary in this study aligns with earlier viewpoints that the slowness of marine biodiversity accumulation during the late Cambrian and the Early Ordovician was linked to widespread oceanic anoxia.