Background: Helicobacter pylori (H. pylori) is one of the strongest risk factors for gastric cancer, and infects more than half of the world population. Globally, the prevalence of H. pylori in patients with an ulcer or non-ulcer dyspepsia is high. Similarly, Kingdom of Saudi Arabia (KSA) is suffering from a challenging prevalence of H. pylori in patients with dyspepsia. In south-west Saudi Arabia, the prevalence of H. pylori infection has been reported to be 54.9%. This paper determines the prevalence of H. pylori infection in patients with dyspepsia in the central rural region of KSA. This study will assist in formulating appropriate healthcare policies at the national level to eradicate H. pylori from the KSA population, relieving sufferers of cumbersome upper abdominal discomfort. Methodology: This prospective study was conducted in the period from May 2016 to November 2017. A total of 686 patients were included. The authors utilized the ROME IV criteria for dyspepsia to screen patients who might have an H.pylori infection, and confirmed the infection using the urea breath test. This prospective study was conducted in the outpatient section of the gastroenterology clinic at Prince Sattam bin Abulaziz University (PSAU) and King Khaled Hospital (KKH). The primary aim of this study was to investigate the frequency of H. pylori infection in patients with dyspepsia in the central rural region of Saudi Arabia. Results: 686 patients fulfilled the ROME IV criteria for dyspepsia and went on to undergo urea breath testing. The male to female ratio of patients was 1.25:1. 39.5% of all patients who were ROME IV positive for dyspepsia, turned out to have an H. pylori infection. Conclusions: The results warrant an evaluation of risk factors associated with the high prevalence of H. pylori in the urban population of KSA in order to reduce upper GIT discomfort and the incidence of gastric cancer. Therefore, it is recommended that further studies be carried out with a specific focus on evaluating the risk factors associated with H. pylori infection in the urban population of KSA.