Abstract Cloud-to-ground (CG) lightning substantially impacts human health and property. However, the relations between U.S. lightning activity and the Madden–Julian oscillation (MJO) and El Niño–Southern Oscillation (ENSO), two predictable drivers of global climate variability, remain uncertain, in part because most lightning datasets have short records that cannot robustly reveal MJO- and ENSO-related patterns. To overcome this limitation, we developed an empirical model of 6-hourly lightning flash count over the contiguous United States (CONUS) using environmental variables (convective available potential energy and precipitation) and National Lightning Detection Network data for 2003–16. This model is shown to reproduce the observed daily and seasonal variability of lightning over most of CONUS. Then, the empirical model was applied to construct a proxy lightning dataset for the period 1979–2021, which was used to investigate the summer MJO–lightning relationship at daily resolution and the winter–spring ENSO–lightning relationship at seasonal resolution. Overall, no robust relationship between MJO phase and lightning patterns was found when seasonality was taken into consideration. El Niño is associated with increased lightning activity over the coastal Southeast United States during early winter, the Southwest during winter through spring, and the Northwest during late spring, whereas La Niña is associated with increased lightning activity over the Tennessee River valley during winter. Significance Statement Cloud-to-ground lightning is dangerous for humans via direct strikes or through triggering wildfires, generating air pollution, etc. How lightning activity can be affected by climate remains unclear, and it is challenging to study their links because the data record for lightning is short. With the available lightning record, we developed a model that relates lightning flash counts over the United States to environmental factors. This model well represents observed fluctuations in daily and seasonal lightning over most of the United States. Because the model only needs environmental information to predict lightning flash counts, we were able to construct a longer record of predicted lightning based on the longer data record of environmental variables. With this dataset, we investigated the links between lightning and climate and found that the state of sea surface temperatures in the tropical Pacific (El Niño–Southern Oscillation) is linked to changes in U.S. lightning patterns in winter and spring.