We synthesize research from complementary scientific fields to address the likely extent and duration of the proposed Anthropocene epoch. Ongoing intensification of human-forced climate change began in the mid-20th century, with steepening increases in greenhouse gases, ocean acidification, global temperature and sea level, along with the restructuring of Earth’s biota. The resulting distinction between relatively stable Holocene conditions and those of the proposed Anthropocene epoch is substantial, irreversible, and likely to persist indefinitely. The still-rising trajectory of greenhouse gas emissions from the energy requirements of a growing global population is leading to yet greater and more permanent divergence of the Anthropocene from the Holocene Earth System. We focus here on the effects of the ensuing climate transformation and its impact on the likely duration of this novel state of the Earth System. Given the magnitude and rapid rise of atmospheric carbon dioxide (CO2), its long lifetime in the atmosphere, and the present disequilibrium in Earth’s energy budget (expressed as the Earth’s Energy Imbalance, or EEI), both temperatures and sea level must continue to rise – even if carbon emissions were lowered to net zero (where CO2 emissions = CO2 removals) – until the energy budget balance is eventually restored. Even if net zero were achieved immediately, elevated global temperatures would persist for at least several tens of millennia. The expected levels of warmth have not been seen since the early Late Pliocene, and interglacial conditions are likely to persist for at least 50,000 years from now under already-accumulated CO2 emissions and Earth’s low eccentricity orbit. Continued increases in greenhouse gas emissions are likely to extend that persistence to around 500,000 years and will likely suppress the pronounced expression of Milankovitch cyclicity typical of the Pleistocene Epoch. This major perturbation alone is sufficient to justify the Anthropocene as an epoch terminating the Holocene Epoch; the wider effects of climate change in driving further, mostly irreversible, restructuring of the biosphere amplifies this distinction.