The rapid growth of unconventional natural gas development (UNGD), also known as hydraulic fracturing, has raised concerns of potential exposures to hazardous chemicals. Few studies have examined the risk of childhood cancer from exposure to UNGD. A case–control study included 498 children diagnosed with leukemia, lymphoma, central nervous system neoplasms, and malignant bone tumors during the period 2010–2019 identified through the Pennsylvania Cancer Registry. Cases were matched to controls using Pennsylvania birth records. For each subject, a new overall UNGD exposure metric was calculated which incorporates both spatial (proximity) and temporal (duration) aspects of well activity. Conditional logistic regression models were used to estimate the risk of combined and individual cancers by overall UNGD exposure, and well proximity. Children with a higher overall UNGD exposure (3rd/4th quartiles) had an increased risk for the four malignancies combined [OR] 1.69 (95% CI 1.01, 2.82) and 1.79 (95% CI 1.00, 3.19) compared to non-exposed children. Overall, individuals living within 0.5 miles of a UNGD site were 3.94 times (95% CI 1.66, 9.30) more likely to develop a malignancy compared to non-exposed children and the risk of lymphoma within 0.5 miles and 0.5–1 miles was also elevated [ORs of 5.05 (95% CI 1.09, 23.39) and 7.71 (95% CI 1.01, 59.00), respectively] compared to non-exposed. Our study found that overall UNGD cumulative activity as well as a proximity to UNGD wells were associated with an increased risk of childhood lymphoma and overall childhood cancers combined.