N,O-Diacylethanolamines (DAEs), derived by the O-acylation of bioactive N-acylethanolamines (NAEs), are most likely present in biological membranes. In the present study, a homologous series of mixed chain DAEs with an N-palmitoyl chain and varying O-acyl chains (n = 6–16) have been synthesized and characterized. Differential scanning calorimetry (DSC) studies revealed a nonclassical type of odd–even alternation in the enthalpy and entropy of melting, with the odd–even effect becoming more prominent with increase in the O-acyl chain length. This was rationalized by analyzing the 3-dimensional structures of several DAEs. In most cases, two types of packing polymorphs (α and β) were observed; while the α polymorph is characterized by a mixed type of chain packing, in the β polymorph the chain packing is symmetric. Analysis of the crystal structures revealed that the odd–even effect is manifested through differences in the packing of acyl chains, with the packing being closer when both chains are even. A possible role of polymorphism in the odd–even effect has also been considered, and it was suggested that the nonclassical behavior observed in the alternation could be attributed to the presence of different fractions of the α and β forms in the bulk mixture. Similar nonclassical odd–even effects and polymorphism may exist in other mixed chain systems, which adopt an “L” shape.