Growers seeking alternatives to traditional polyethylene plastic mulch may use biodegradable plastic mulches (BDMs). However, plasticulture systems typically also use plastic drip tape underneath the mulch, which must be removed from the field and disposed of at the end of the season, making tilling the BDM into the soil more difficult and expensive. A potential solution to this dilemma may be to use other irrigation methods, such as overhead sprinklers, that could be more easily removed from the field and reused from year to year. At Knoxville, TN, in 2019 and 2020, we grew three cultivars of romaine lettuce (Lactuca sativa) on BDM with two irrigation systems (overhead sprinklers above the mulch and drip irrigation tape under the mulch) to compare water use, disease, and yield in these two irrigation systems. Water use was higher in overhead vs. drip irrigation in both years; however, the difference in water use was much smaller in 2019 due to higher rainfall amounts during the time period the lettuce was growing in the field (March to May). Disease incidence and severity were very low both years for both irrigation systems. There were no differences in marketable yield (number of heads) between irrigation treatment in 2019. In 2020, marketable yield by number was greater in the drip vs. overhead irrigation treatment. Unmarketable yield in 2019 was due to heads that were too small; in 2020, unmarketability was predominantly due to tipburn in overhead irrigated ‘Jericho’. Overall, marketable lettuce yield did not differ between irrigation treatments in 2019 and was similar for ‘Parris Island Cos’ in 2020. Although quantitative weed counts were not made, observations of weed pressure between rows showed that weed pressure was higher in overhead irrigated compared with drip irrigated subplots. This highlights the need to have a between-row weed management program in place. The results of this study suggest that with attention to cultivar and weed management, overhead irrigation could be a viable alternative to drip irrigation for lettuce production on BDM, especially for early spring lettuce when rainfall is historically more plentiful.