The Hylocereus species that are grown as exotic fruit crops are very often farmed under marginal agronomic conditions, which may include exposure to high temperatures. Here we present a pioneering investigation of grafting as an agro-technique to improve heat tolerance in Hylocereus. To this end, we studied the diploid species H. undatus, the tetraploid H. megalanthus and its di-haploid gamete-derived line 2719, and the interspecific-interploid tetraploid Z-10, all grafted onto H. undatus as the rootstock. Self-grafted, grafted and non-grafted plants were acclimated for one week (to obtain baseline values) and then exposed to heat stress (45/35 °C day/night) for three days, followed by a one-week recovery period under optimal temperatures (30/22 °C). A comparison of the physiological, biochemical and molecular performances of the grafted and self-grafted plants under heat stress and during the recovery period vs those of non-stressed plants (control; 30/22 °C) showed that the grafted and self-grafted plants performed better in most of the assessments: grafted and self-grafted plants recovered more rapidly from the heat stress and suffered far less stem damage. An unexpected – but important – finding that may have implications for other crop was that the self-grafted plants showed better performance than non-grafted plants throughout the trial. Our findings provide support for grafting as a strategy for coping with the stress induced by extremely high temperatures. This study thus paves the way for further investigations of grafting in Hylocereus as a valuable technique that will maintain crop productivity in the face of increasing worldwide temperatures.