Reduced heart rate variability (HRV) is an autonomic nervous system (ANS) response that may indicate dysfunction in the human body. Consistent evidence shows cancer patients elicit lower HRV; however, only select cancer locations were previously evaluated. Thus, the aim of the current study was to explore HRV patterns in patients diagnosed with and in varying stages of the most prevalent cancers. At a single tertiary academic medical center, 798 patients were recruited. HRV was measured via an armband monitor (Warfighter MonitorTM, Tiger Tech Solutions, Inc., Miami, FL, USA) equipped with electrocardiographic capabilities and was recorded for 5 to 7 min with patients seated in an upright position. Three time-domain metrics were calculated: SDNN (standard deviation of the NN interval), rMSSD (the root mean square of successive differences of NN intervals), and the percentage of time in which the change in successive NN intervals exceeds 50ms within a measurement (pNN50). Of the 798 patients, 399 were diagnosed with cancer. Cancer diagnoses were obtained via medical records one week following the measurement. Analysis of variance models were performed comparing the HRV patterns between different cancers, cancer stages (I–IV), and demographic strata. A total of 85% of the cancer patients had breast, gastrointestinal, genitourinary, or respiratory cancer. The cancer patients were compared to a control non-cancer patient population with similar patient size and distributions for sex, age, body mass index, and co-morbidities. For all HRV metrics, non-cancer patients exhibited significantly higher rMSSDs (11.1 to 13.9 ms, p < 0.0001), SDNNs (22.8 to 27.7 ms, p < 0.0001), and pNN50s (6.2 to 8.1%, p < 0.0001) compared to stage I or II cancer patients. This significant trend was consistently observed across each cancer location. Similarly, compared to patients with stage III or IV cancer, non-cancer patients possessed lower HRs (−11.8 to −14.0 bpm, p < 0.0001) and higher rMSSDs (+31.7 to +32.8 ms, p < 0.0001), SDNNs (+45.2 to +45.8 ms), p < 0.0001, and pNN50s (19.2 to 21.6%, p < 0.0001). The HR and HRV patterns observed did not significantly differ between cancer locations (p = 0.96 to 1.00). The depressed HRVs observed uniformly across the most prevalent cancer locations and stages appeared to occur independent of patients’ co-morbidities. This finding highlights the potentially effective use of HRV as a non-invasive tool for determining common cancer locations and their respective stages. More studies are needed to delineate the HRV patterns across different ages, between sexes and race/ethnic groups.