Changes in carbon and sulfur cycling over geologic time may have caused considerable modification of atmospheric and oceanic composition and climate. Here we calculate pyrite sulfur (Spy) and organic carbon (Corg) burial rates from recently improved Cenozoic stable isotope records, and from these rates we infer global changes in Corg burial environments. Given predominantly normal shelf-delta organic carbon burial, the global Spy burial flux should be coupled to Corg burial. However, we find that the major early Cenozoic peak in Corg burial coincides with a minimum in Spy burial. Although the calculated magnitude of variations in global pyrite burial flux is sensitive to our assumptions about the concentration of sulfate in paleoseawater, a non-steady-state isotope mass balance model indicates very low Spy burial rates during the Paleocene and a dramatic increase starting near the Paleocene-Eocene boundary, dropping off to a fairly constant Cenozoic rate beginning in the middle Eocene. High Corg/Spy burial ratios (C/S mole ratio ≈15–30) coinciding with the Paleocene carbon isotope maximum most likely reflect enhanced accumulation of terrestrial organic carbon in Paleocene terrestrial swamps. We suggest that rapid burning of accumulated Paleocene terrestrial organic carbon could have significantly contributed to the short-lived negative carbon isotope excursion at the Paleocene-Eocene boundary in addition to or possibly even as an alternative to release of gas hydrates from the continental slopes. An early Eocene minimum in calculated Corg/Spy burial ratios (C/S mole ratio ≈2–4) suggests that the predominant locus of organic carbon burial shifted to euxinic environments in a warm early Eocene ocean.