Introduction Increasing life expectancy has led to a higher incidence of cancer in the elderly, thus making them vulnerable and worsening their health-related quality of life (HRQoL) and their need for support. Objective The aim of this study was to examine the HRQoL and social support in elderly Greek lung and gastrointestinal cancer patients undergoing chemotherapy. Methods This was a descriptive, cross-sectional study of 104 elderly cancer patients, who were receiving chemotherapy in the outpatient department and inpatient ward of a General Hospital in Athens. The data were collected using purposive sampling between December 2019 and May 2020, and included demographic and clinical characteristics, the HRQoL questionnaire, Short Form 36 (SF36), and the Personal Resource Questionnaire (PRQ-2000). Results The participants' median age was 72 years; the majority were male (62.5%) and had lung cancer (57.7%). The SF36 data revealed a relatively moderate (42.7–62.61) HRQoL in most subscales. The “Pain” subscale recorded the highest score (75.0), and the “social function” subscale the lowest (42.79). The PQR-2000 indicated a satisfactory level of social support (81.65), with values ranging between 48 and 105; married patients with higher education scored more highly ( p < .05). Patients aged 65–75 years reported better HRQoL and greater social support than older patients. In addition, patients with their own family and a relatively high income reported better HRQoL and social support compared to single individuals, with low income, who were cared for by their children. Positive and statistically significant ( p < .05) correlations were found between the SF36 subscales of role functioning/physical, vitality, general health, emotional well-being and the PRQ-2000. Conclusion The HRQoL and social support of elderly cancer patients positively affect the course of their health. Healthcare systems and social services should address the multiplying needs of these patients with targeted interventions to support their well-being.