Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis. Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth with increased levels of hexoses, particularly galactose, as well as the pectin abundance in cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter, and electrophoretic mobility shift assays all demonstrated that a UDP-glucose 4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in expression of the A. thaliana homolog, AtUGE2-4, in response to LcERF2 over-expression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to the LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism and thus pedicel growth, in part by repressing the expression of LcUGE.