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Abstract In 2021, the US Surgeon General issued a national advisory citing an epidemic of isolation and loneliness. Even before the onset of the COVID-19 pandemic, approximately half of people in the US reported experiencing measurable levels of loneliness. Despite localized and select cross-sectional studies highlighting even higher increases in isolation/loneliness during the COVID-19 pandemic, additional research is needed, particularly for youth and young adults. This work examines patterns of isolation/loneliness across the US from 2016 to 2022 among individuals aged 24 and younger. Our study leverages a unique dataset, Crisis Text Line, which provides complete spatiotemporal coverage of crisis conversations in the US. We conducted a geospatial analysis using Kuldroff’s Space–Time SatScan to identify statistically significant clustering of elevated isolation/loneliness-related conversations. The statistical significance of spatiotemporal clusters was determined using Monte Carlo simulations (n = 9999). Results demonstrated local relative risk as high as 1.47 in high-risk populations in Southern, Midwest, and Atlantic states, indicating areas where the actual case count is 147% of the expected cases (pvalue < 0.01) from May to July 2020. Results also identified co-occurrence of isolation/loneliness and other crises concerns, including depression/sadness, anxiety, and multiple suicidality indicators, with higher rates among racial/ethnic minority, transgender and gender diverse, and younger individuals. This work makes a unique contribution to the literature by elucidating spatiotemporal disparities in isolation/loneliness among young people, providing much-needed knowledge as to where future public health interventions are immediately needed.