Stripe rust caused by Puccnina striiformis (Pst) is an economically important disease attacking wheat all over the world. Identifying and deploying new genes for Pst resistance is an economical and long-term strategy for controlling Pst. A genome-wide association study (GWAS) using single nucleotide polymorphisms (SNPs) and functional haplotypes were used to identify loci associated with stripe rust resistance in synthetic-derived (SYN-DER) wheats in four environments. In total, 92 quantitative trait nucleotides (QTNs) distributed over 65 different loci were associated with resistance to Pst at seedling and adult plant stages. Nine additional loci were discovered by the linkage disequilibrium-based haplotype-GWAS approach. The durable rust-resistant gene Lr34/Yr18 provided resistance in all four environments, and against all the five Pst races used in this study. The analysis identified several SYN-DER accessions that carried major genes: either Yr24/Yr26 or Yr32. New loci were also identified on chr2B, chr5B, and chr7D, and 14 QTNs and three haplotypes identified on the D-genome possibly carry new alleles of the known genes contributed by the Ae. tauschii founders. We also evaluated eleven different models for genomic prediction of Pst resistance, and a prediction accuracy up to 0.85 was achieved for an adult plant resistance, however, genomic prediction for seedling resistance remained very low. A meta-analysis based on a large number of existing GWAS would enhance the identification of new genes and loci for stripe rust resistance in wheat. The genetic framework elucidated here for stripe rust resistance in SYN-DER identified the novel loci for resistance to Pst assembled in adapted genetic backgrounds.