Background: Colorectal cancer (CRC) poses a major health challenge worldwide, specifically in developing countries, where late-stage diagnoses lead to substantial mortality rates. This study aims to evaluate CRC knowledge and screening behaviors in Pakistan while identifying barriers that hinder CRC screening uptake. Materials and methods: In this cross-sectional study, a paper questionnaire was distributed to patients and companions in hospitals across all provinces in Pakistan between March 2022 and December 2023. Results: Out of 5,244 participants (68.7% male), only 23.2% claimed knowledge of CRC, while 31.5% had some awareness of it. Merely 20.1% believed CRC to be common in Pakistan. Only 6.6% of those aged 50 and above had undergone CRC screening, with 59.7% reporting no prior screening. Notably, 35.9% expressed interest in colonoscopy at age 45 for CRC screening. Screening intentions were lower in younger, female participants, and residents from Balochistan compared to their counterparts. Widowed/divorced individuals showed higher intentions than married ones. Several barriers, including a lack of screening facilities and fear of results, negatively impacted screening intentions. Conclusion: Colorectal cancer awareness and screening uptake remain critically low in Pakistan, with significant barriers including a lack of knowledge, physician recommendation, and access to screening facilities. Sociodemographic factors such as age, gender, education, and region significantly influenced screening intentions. Targeted awareness efforts and improved healthcare provider engagement are essential to enhance CRC screening rates and reduce the disease burden.