This proceedings volume compiles selected, revised papers presented at the 53rd SouthEastern International Conference on Combinatorics, Graph Theory, and Computing (SEICCGTC 2022), which took place at Florida Atlantic University in Boca Raton, USA, from March 7th to 11th, 2022. The SEICCGTC is widely regarded as a trendsetter for other conferences worldwide. Many ideas and themes initially discussed here have subsequently been explored in other conferences and symposia. Since 1970, the conference has been held annually in Baton Rouge, Louisiana, and Boca Raton, Florida. Over the years, it has grown to become the primary annual conference in its fields, playing a crucial role in disseminating results and fostering collaborative work. This volume is tailored for the community of pure and applied mathematicians in academia, industry, and government, who work in combinatorics and graph theory, as well as related areas of computer science and the intersections among these fields.