Background: Coping with the current and future burden of cancer requires an in-depth understanding of cancer incidence and death trends. As of 2020, breast, lung, prostate, and colorectal cancer are the most incident cancers, while lung, colorectal, pancreas, and breast cancer result in the most deaths. Here we integrate observed cancer statistics and trends with observed and estimated US demographic data to project cancer incidences and deaths to the year 2040. Methods: Demographic cancer-specific delay-adjusted incidence and death rates from the Surveillance, Epidemiology, and End Results Program (2014-2016) were combined with US Census Bureau population growth projections (2016) and average annual percentage changes in incidence (2011-2015) and death (2012-2016) rates to project cancer incidences and deaths through the year 2040. We examined the 10 most incident and deadly cancers as of 2020. We utilized Joinpoint analysis to examine changes in incidence and death rates over time relative to changes in screening guidelines. Results: We predict the most incident cancers in 2040 in the US will be breast (322,000 diagnoses in 2040) and lung (182,000 diagnoses in 2040) cancer. Continuing decades long observed incident rate trends we predict that melanoma (173,000 diagnoses in 2040) will become the 3^rd most common cancer while prostate cancer (63,000 diagnoses in 2040) will become the 5^th most common cancer after colorectal cancer (139,000 diagnoses in 2040). Lung cancer (61,000 deaths in 2040) is predicted to continue to be the leading cause of cancer related death, with pancreas (45,000 deaths in 2040) and liver & intrahepatic bile duct (38,000 deaths in 2040) cancer surpassing colorectal cancer (34,000 deaths in 2040) to become the second and third most common causes of cancer related death, respectively. Breast cancer deaths (29,000 in 2040) are predicted to continue to decrease and become the fifth most common cause of cancer death. Joinpoint analysis of incidence and death rates supports a significant past, present, and future impact of cancer screening programs on the number of cancer diagnoses and deaths, particularly for prostate, thyroid, melanoma incidences, and lung cancer deaths. Conclusions: We demonstrate marked changes in the predicted landscape of cancer incidence and deaths by 2040. Our analysis reveals an influence of cancer screening programs on the number of cancer diagnoses and deaths in future years. These projections are important to guide future research funding allocations, healthcare planning, and health policy efforts.