Background and Aim Because genetic and geographic variations in intestinal microbiota are known to exist, the focus of this study was to establish an estimation of microbiota in colorectal cancer (CRC) patients in Saudi Arabia by means of metagenomic studies. Methods From July 2010 to November 2012, colorectal cancer patients attending our hospital were enrolled for the metagenomic studies. All underwent clinical, endoscopic, and histological assessment. Mucosal microbiota samples were collected from each patient by jet-flushing colonic mucosa with distilled water at unified segments of the colon, followed by aspiration, during colonoscopy. Total purified dsDNA was extracted and quantified prior to metagenomic sequencing using an Illumina platform. Satisfactory DNA samples (n = 29) were subjected to metagenomics studies, followed by comprehensive comparative phylogenetic analysis. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota. Results Metagenomics data on 29 patients (14 females) in the age range 38–77 years were analyzed. The majority 11 (37%) of our patients were overweight (BMI = 25–30). Rectal bleeding was the presenting symptom in 18/29 (62%), while symptomatic anemia was the presenting symptom in 11/29 (37%). The location of colon cancer was rectal in 14 (48%), while cecal growth was observed in 8 (27%). Hepatic flexure growth was found in 1 (3%), descending colonic growth was found in 2 (6%), and 4 (13%) patients had transverse colon growth. The metagenomics analysis was carried out, and a total of 3.58G reads were sequenced, and about 321.91G data were used in the analysis. This study identified 11 genera specific to colorectal cancer patients when compared to genera in the control group. Bacteroides fragilis and Fusobacterium were found to be significantly prevalent in the carcinoma group when compared to the control group. Conclusion The current study has given an insight into the microbiota of colorectal cancer patients in Saudi Arabia and has identified various genera significantly present in these patients when compared to those of the control group.