Background: In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50–69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods: A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results: For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011–2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions: The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.