This study examined colorectal cancer (CRC) knowledge and the relationship between knowledge, risk factors and screening behaviors among African Americans and Whites in the Deep South. One hundred and twenty three African Americans and Whites age-eligible for CRC screening were interviewed by telephone survey as part of a church-based CRC educational intervention. CRC knowledge was lower among those with less education, unemployed, Medicaid, Medicare, and less family income. Generally, participants who had more CRC knowledge were more likely to have engaged in screening behaviors. Participants who had a family history of CRC were more likely to have had a fecal occult blood test (OR = 2.55, 0.99-6.60) or barium enema (OR = 3.84, 1.44-10.24) than those without. Whites were more likely to have had a flexible sigmoidoscopy (OR = 4.17, 1.09-16.67), colonoscopy (OR = 7.14, 1.72-25) or barium enema (OR = 6.25, 1.67-25) than African Americans. Church-based CRC screening intervention programs should target African Americans, those with no family history of CRC, and those with less education.