The use of plastic biodegradable mulch (BDM) in many vegetable crops such as tomato (Solanum lycopersicum L.), broccoli (Brassica oleracea L. var. italica), and pepper (Capsicum annuum L.) has been proven to be of equal benefit as polyethylene (PE) mulch. However, there are limited research findings on the performance of BDM with a large fruited crop such as pumpkin (Cucurbita pepo L.) where the fruit can rest directly on the mulch for an extended period. To investigate whether heavy fruit might cause the mulch to degrade more quickly than expected, thereby, influencing weed control, fruit yield, and fruit quality including mulch adhesion on fruit, we carried out a field experiment in 2015 and 2016 at two locations in the United States with distinctive climates, Mount Vernon, WA and Knoxville, TN. Three plastic mulches marketed as biodegradable (BioAgri, Organix, and Naturecycle), one fully biodegradable paper mulch (WeedGuardPlus), and one experimental plastic BDM consisting of polylactic acid and polyhydroxyalkanoates (Exp. PLA/PHA) were evaluated against PE mulch and bare ground where ‘Cinnamon Girl’ pie pumpkin was the test crop. There was significant weed pressure in the bare ground plots at both locations over both years, indicating viable weed seed banks at the field sites. Even so, weed pressure was minimal across mulch treatments at both locations over both years because the mulches remained sufficiently intact during the growing season. The exceptions were Naturecycle in 2015 at both locations because of the splitting of the mulch and consequently higher percent soil exposure (PSE), and the penetration of all the plastic mulches at Knoxville by nutsedge (Cyperus sp. L.); nutsedge did not penetrate WeedGuardPlus. At Mount Vernon, overall pumpkin yield across both years averaged 18.1 t·ha−1, and pumpkin yield was the greatest with PE, Exp. PLA/PHA, BioAgri, and Naturecycle (19.9–22.8 t·ha−1), intermediate with Organix and WeedGuardPlus (15.3–18.4 t·ha−1), and the lowest for bare ground (8.7 t·ha−1). At Knoxville, overall pumpkin yield across both years averaged 17.7 t·ha−1, and pumpkin yield did not differ because of treatment (15.3–20.4 t·ha−1). The differences in yield between treatments at Mount Vernon were likely because of differences in the soil temperature. At 10 cm depth, the average soil temperature was 1 °C lower for bare ground and WeedGuardPlus as compared with PE mulch and plastic BDMs (20.8 °C). In contrast, soil temperatures were generally higher (25.2 to 28.3 °C) for all treatments at Knoxville and more favorable to crop yield compared with Mount Vernon. Forty-two percent to 59% of pumpkin fruit had mulch adhesion at harvest at Mount Vernon, whereas only 3% to 12% of fruit had mulch adhesion at Knoxville. This difference was because of the location of fruit set—at Mount Vernon, most of the fruit set was on the mulch whereas at Knoxville, vine growth was more extensive and fruit set was mostly in row alleys. Fruit quality differences among treatments were minimal during storage across both locations and years except for total soluble solids (TSS) in 2016, which was lower for bare ground and WeedGuardPlus compared with all the plastic mulches. Taken overall, these results indicate that pie pumpkin grown with BDM has fruit yield and quality comparable to PE mulch; however, adhesion of some BDMs on fruit could affect marketable yield. Furthermore, paper mulch appears to prevent nutsedge penetration.