Fresh-cut lettuce (Lactuca sativa) packaged as salad mixes are increasingly popular to consumers but are highly perishable. Cultivars bred with extended shelf life could increase overall production efficiency by reducing the frequency of product replacement in the marketplace. Understanding the inheritance of shelf life is needed to develop efficient breeding strategies for this trait. A population of 95 recombinant inbred lines (RILs) from slow-decaying ‘Salinas 88’ × rapidly decaying ‘La Brillante’ was grown in four field experiments. Cut lettuce was evaluated for decay in modified atmosphere (MA) packages flushed with N2 or air (control). Correlations between field experiments ranged from 0.47 to 0.84 (P < 0.01). Three quantitative trait loci (QTL) for decay of cut lettuce were detected on linkage groups (LGs) 1, 4, and 9 with ‘Salinas 88’ alleles associated with slower decay. The QTL on LG 4 (qSL4) was a major determinant of decay explaining 40% to 74% of the total phenotypic variance of the trait. The greatest effect of this QTL was observed between 29 and 50 days after harvest. QTL × environment interactions contributed less than 14% to the total variation. RILs with the ‘Salinas 88’ allele of qSL4 had slower decay when packaged in air compared with N2, whereas no difference between air and N2 packaging was detected with the ‘La Brillante’ allele. A subset of RILs with either the ‘Salinas 88’ or ‘La Brillante’ allele of qSL4 was grown in two field experiments and evaluated for decay of whole heads. Genetic variation among RILs for whole-head decay was found but could not be attributed to qSL4. Decay of cut lettuce in ‘Salinas 88’ × ‘La Brillante’ is a highly heritable trait conditioned by a few QTL and phenotypic selection is likely to be effective. However, shelf life evaluations are time-consuming, destructive, and require large amounts of field-grown lettuce. Therefore, qSL4 is a good QTL to develop molecular markers for marker-assisted selection. The mechanism of decay controlled by qSL4 is unknown but appears to be specific to cut lettuce and may have allele specific interactions with packaging atmospheric compositions.