Introduction: Helicobacter pylori (H. pylori) infection is a common chronic bacterial infection globally, particularly prevalent in developing countries. It is associated with gastrointestinal disorders such as dyspepsia, peptic ulcer disease, and gastric malignancies. Dyspepsia, characterized by upper abdominal discomfort, pain, bloating, nausea, and early satiety, is a frequent complaint in gastrointestinal clinics. Accurate diagnosis and management of H. pylori infection in dyspeptic patients are crucial for effective treatment and complication prevention. This study aims to assess the prevalence of H. pylori infection in dyspeptic patients at a rural tertiary care center and to explore the correlation of various symptoms with H. pylori infection. Methods: This prospective observational study was conducted at Chettinad Hospital and Research Institute, involving 75 patients with dyspepsia who underwent upper gastrointestinal endoscopy. Patients aged 16 to 80 years were included, with exclusions for those on proton pump inhibitor or antibiotic therapy within the past month. Endoscopic biopsies were taken and analyzed histopathologically. Data on demographics, symptoms, and endoscopic findings were collected and analyzed using descriptive statistics, Pearson’s chi-square test, logistic regression, and Spearman’s rank correlation. Results: The prevalence of H. pylori infection was 53.33%. The highest prevalence was in the 31-45 years age group (30%), followed by the 18-30 years and 46-60 years groups (25% each), and the 61-75 years group (20%). Males had a higher prevalence (60%) compared to females (40%). Symptoms such as upper abdominal pain (75%), bloating (62.5%), and fatty food intolerance (50%) were significantly associated with H. pylori infection. Gastritis was the most common endoscopic abnormality (50%), followed by GERD (25%). Logistic regression identified upper abdominal pain and bloating as significant independent predictors of H. pylori infection. Spearman’s rank correlation showed significant associations between the severity of symptoms and histopathological grading of H. pylori. Conclusion: The study found a significant prevalence of H. pylori infection in dyspeptic patients at a rural tertiary care center, particularly among middle-aged males. Upper abdominal pain, bloating, and fatty food intolerance were the most common symptoms associated with the infection. Gastritis was the predominant endoscopic finding in infected patients. These results underscore the need for routine screening and targeted management of dyspeptic patients to improve clinical outcomes. Future research should focus on multi-center studies, long-term follow-up, and exploring the influence of socioeconomic and environmental factors on H. pylori infection.