The El Nino Southern Oscillation (ENSO) phenomenon is devastating as it negatively impacts global climatic conditions, which can cause extreme events, including floods and droughts, which are harmful to the region’s economy. Pakistan is also considered one of the climate change hotspot regions in the world. Therefore, the present study investigates the effect of the ENSO on extreme precipitation events across the Upper Indus Basin. We examined the connections between 11 extreme precipitation indices (EPIs) and two ENSO indicators, the Southern Oscillation Index (SOI) and the Oceanic Niño Index (ONI). This analysis covers both annual and seasonal scales and spans the period from 1971 to 2019. Statistical tests (i.e., Mann–Kendall (MK) and Innovative Trend Analysis (ITA)) were used to observe the variations in the EPIs. The results revealed that the number of Consecutive Dry Days (CDDs) is increasing more than Consecutive Wet Days (CWDs); overall, the EPIs exhibited increasing trends, except for the Rx1 (max. 1-day precipitation) and Rx5 (max. 5-day precipitation) indices. The ENSO indicator ONI is a temperature-related ENSO index. The results further showed that the CDD value has a significant positive correlation with the SOI for most of the UIB (Upper Indus Basin) region, whereas for the CWD value, high elevated stations gave a positive relationship. A significant negative relationship was observed for the lower portion of the UIB. The Rx1 and Rx5 indices were observed to have a negative relationship with the SOI, indicating that El Nino causes heavy rainfall. The R95p (very wet days) and R99p (extreme wet days) indices were observed to have significant negative trends in most of the UIB. In contrast, high elevated stations depicted a significant positive relationship that indicates they are affected by La Nina conditions. The PRCPTOT index exhibited a negative relationship with the SOI, revealing that the El Nino phase causes wet conditions in the UIB. The ONI gave a significant positive relationship for the UIB region, reinforcing the idea that both indices exhibit more precipitation during El Nino. The above observations imply that while policies are being developed to cope with climate change impacts, the effects of the ENSO should also be considered.