WRKYs represent a large family of plant transcription factors characterized by a highly conserved WRKY domain. WRKY transcription factors are important for plant growth, development, and responses to environmental stresses. However, this family has not been previously identified in Sesuvium portulacastrum, a typical halophyte that grows in saline soils and coastal marshlands and contributes to the stability of coastal ecosystems. Here, we identified 68 SpWRKYs from S. portulacastrum and classified them into six subclades. These genes were unevenly distributed across twenty-two chromosomes and exhibited both intra- and interspecific expansion based on segmental duplication events, orthologous gene pairs, and duplication relationships. All SpWRKY proteins contained at least one conserved WRKY domain, and their promoters contain 33 cis-elements involving abiotic stress signaling, developmental regulation, phytohormone responses, light responsiveness, and tissue-specific expression. Transcriptome analysis under cadmium, copper, and salt stress showed that many SpWRKYs were stress-responsive. Among them, SpWRKY40 and SpWRKY51 showed 3.8-fold and 4.2-fold induction in roots under cadmium treatment, which was further confirmed by quantitative real-time PCR. Subcellular localization and transient expression in tobacco, together with yeast one-hybrid experiments, demonstrated that SpWRKY40 and SpWRKY51 function as transcription activators. They bind specifically to the GTCAA and TTGACC cis-elements. Our study provides a detailed overview of the SpWRKY family and functional insights into SpWRKY40 and SpWRKY51 as transcription activators. The findings offer valuable candidate genes for future applications in improving cadmium stress tolerance in S. portulacastrum and related crop species.