Tropical milkweed (Asclepias curassavica) serves as a host plant for monarch butterflies (Danaus plexippus) and other insect herbivores that can tolerate the abundant cardiac glycosides that are characteristic of this species. Cardiac glycosides, along with additional specialized metabolites, also contribute to the ethnobotanical uses of A. curassavica. To facilitate further research on milkweed metabolism, we assembled the 241 Mbp genome of a fifth-generation inbred line of A. curassavica into 851 contigs, with an N50 of 2.4 Mbp. Scaffolding resulted in 97.9% of the assembly being anchored to 11 chromosomes, which are colinear with the previously assembled common milkweed (A. syriaca) genome. Assembly completeness evaluations showed that 97.9% of the BUSCO gene set is present in the A. curassavica assembly. The transcriptomes of six tissue types (young leaves, mature leaves, stems, flowers, buds, and roots), with and without methyl jasmonate treatment, showed both tissue-specific gene expression and induced expression of genes that may be involved in cardiac glycoside biosynthesis. Together, this genome sequence and transcriptome analysis provide important resources for further investigation of the ecological and medicinal uses of A. curassavica.