The development of rice cultivars with salinity tolerance, high yield, and good quality is a very essential demand that has been raised to provide poor farmers in the lowland conditions of the coastlines of the Mekong Delta, Vietnam. This study aimed to develop rice cultivars that were tolerant of salinity at the seedling and reproductive stages via molecular marker, single crossing, and backcrossing breeding methods. The salt tolerance of F8 and BC3F4 progenies was assessed under salt stress field conditions to select promising lines for improving production by farmers. Salt tolerance alleles on chromosomes 1 and 8 were detected by combining traditional breeding by backcross and generation selection with SSR markers. L1 (OM10252/Pokkali); L5 (OMCS2012/Pokklai); L21 and L22 (OM10252/Pokkali//OM10252); and L24 and L25 (OM8902/Pokkali//OM8902) were identified as high-yielding genotypes with good salinity tolerance. However, many remaining lines failed due to their extended growth duration, high unfilled grain percentage, and poor grain quality. Four lines, namely, viz. L1, L5, L24, and L25, exhibited good agronomic characters, such as low amylose content and salt stress tolerance. The typical tolerant genotype Pokkali was successfully exploited into high-yielding rice cultivars via breeding programs. This work is a good opportunity to improve salt tolerance rice cultivars via marker-assisted selection with RM223, RM8094, HATRI02, RM3412, RM493, and RM3252.