DNA is a widely used biopolymer for the construction of nanoscale objects due to its programmability and structural predictability. DNA oligonucleotides can, however, exhibit a great deal of local structural diversity. DNA conformation is strongly linked to both environmental conditions and the nucleobase identities inherent in the oligonucleotide sequence, but the exact relationship between sequence and local structure is not completely understood. We previously determined the X-ray crystal structure of a DNA 13-mer that forms a continuously hydrogen bonded three-dimensional lattice through Watson-Crick and non-canonical base pairs. In the current work I examined how the sequence of the Watson-Crick duplex region influenced crystallization of this 13-mer. I screened all possible self-complementary sequences in the hexameric duplex region and found 21 oligonucleotides that crystallized. Sequence analysis showed that one specific Watson-Crick base pair influenced the crystallization propensity and the speed of crystal self-assembly. I determined X-ray crystal structures for 13 of these oligonucleotides and found sequence-specific structural changes suggesting that this base pair may serve as a structural anchor during crystal assembly. I explored the crystal self-assembly and nucleation process and demonstrated that crystals grown from mixtures of two different oligonucleotide sequences contained both the oligonucleotides. These results suggested that crystal self-assembly is nucleated by the formation of Watson-Crick duplexes. Finally, I also examined how a single nucleotide addition to the DNA 13-mer leads to a significantly different overall structure under identical crystallization conditions. The 14-mer crystal structures described here showed that all of the predicted Watson-Crick base pairs were present, but the major difference as compared to the parent 13-mer structure was a significant rearrangement of non-canonical base pairs. This included the formation of a sheared A-G base pair, a junction of strands formed from base triple interactions, and tertiary interactions that generated structural features similar to tandem sheared G-A base pairs. The adoption of this alternate non-canonical structure was dependent in part on the sequence of the Watson-Crick duplex region. These results provided important new insights into the sequence/structure relationship of short DNA oligonucleotides and demonstrated a unique interplay between Watson-Crick and non-canonical base pairs that are responsible for crystallization fate.