Measurement of antioxidant activity using biologically relevant assays is important in the screening of fruits for potential health benefits. The cellular antioxidant activity (CAA) assay quantifies antioxidant activity in cell culture and was developed to meet the need for a more biologically representative method than the popular chemistry antioxidant capacity measures. The objective of the study was to determine the cellular antioxidant activity, total phenolic contents, and oxygen radical absorbance capacity (ORAC) values of 25 fruits commonly consumed in the United States. Pomegranate and berries (wild blueberry, blackberry, raspberry, and blueberry) had the highest CAA values, whereas banana and melons had the lowest. Apples were found to be the largest contributors of fruit phenolics to the American diet, and apple and strawberries were the biggest suppliers of cellular antioxidant activity. Increasing fruit consumption is a logical strategy to increase antioxidant intake and decrease oxidative stress and may lead to reduced risk of cancer.