One of the most widely used auxinic herbicides in southern Iran’s cereal crop fields is 2,4-D; however, the concurrent growing season of off-season melons in this region potentially leads to herbicide drift from cereal fields to the melon fields. To study the response of some Iranian wild melon accessions to three simulated drift rates of 2,4-D, including 112.1, 11.2, and 3.7 g ae ha−1, a field experiment was conducted during 2019 and 2020 growing seasons. It was found that by increasing the herbicide rate from 3.7 to 112.1 g ae ha−1, the level of visual injury increased in all accessions. However, significant variation in herbicide tolerance was observed among different melon accessions. The MEL-R1 was the most tolerant accession with only 20% injury, while MEL-D8 displayed very high injury rate (ca. 90%) as assessed at 6 weeks after treatment during 2019. The accession MEL-S3 was the most tolerant to 2,4-D drift rates (20% injury) at 6 weeks after treatment during 2020. There was no significant difference between the accessions MEL-R1 and MEL-S3 in terms of their response to 2,4-D treatment during both years of the study, as these accessions fully recovered from injury over 6 weeks after herbicide treatment. In addition, only these two accessions were able to produce yield after the application of 2,4-D at the highest rate tested (112.1 g ae ha−1). Therefore, the melon accessions MEL-R1 and MEL-S3 could be recommended for cultivation and even for breeding programs in order to develop 2,4-D-tolerant commercial cultivars in regions where this herbicide is commonly used in cereal crop production adjacent to the melon fields.