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The COVID-19 pandemic disrupted healthcare and reduced cancer diagnoses in the U.S., raising concerns about its impact on time-to-treatment initiation (TTI), a critical factor for survival. This study examined the changes in TTI for 1,213,481 individuals newly diagnosed with female breast, non-small cell lung, colon, or rectal cancer between 2019 and 2022, using the National Cancer Database. We compared TTI in 2020-2022 with 2019 by cancer site, diagnosis time of year, stage, and treatment modality. In 2020, TTI significantly decreased for all cancers compared to 2019, especially in the second quarter (2.97 to 4.29 days). However, TTI increased across sites in 2021 (0.31 to 2.15 days) and in 2022 (1.43 to 5.07 days). Reduced diagnoses and efforts to prioritize cancer care during the pandemic may partly explain observed TTI decreases, whereas workforce constraints likely contributed to the later increases. Ongoing evaluation of TTI and associations with patient outcomes is warranted., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)