We quantify weekly methane emissions at 0.25∘ × 0.3125∘ (≈25 × 25 km2) resolution from the Permian Basin, the largest oil production basin in the US, by inverse analysis of satellite observations from the TROPOspheric Monitoring Instrument (TROPOMI) from May 2018 to October 2020. The mean oil and gas emission from the region (± standard deviation of weekly estimates) was 3.7 ± 0.9 Tg a−1, higher than previous TROPOMI inversion estimates that may have used biased prior emissions or background assumptions. We find strong week-to-week variability in emissions superimposed on longer-term trends, and these are consistent with independent inferences of temporal emission variability from tower, aircraft, and multispectral satellite data. New well development and natural gas spot price were significant drivers of variability in emissions over our study period but the concurrent 50 % increase in oil and gas production was not. The methane intensity (methane emitted per unit of methane gas produced) averaged 4.6 % ± 1.3 % and steadily decreased from 5 %–6 % in 2018 to 3 %–4 % in 2020. While the decreasing trend suggests improvement in operator practices during the study period, methane emissions from the Permian Basin remained high, with methane intensity an order of magnitude above the industry target of <0.2 %. Our success in using TROPOMI satellite observations for weekly estimates of emissions from a major oil production basin shows promise for application to near-real-time monitoring in support of climate change mitigation efforts.