One of the major concerns that receive global attention is the presence of organic pollutants (dyes, pharmaceuticals, pesticides, phenolic compounds, heavy metals, and so on), originating from various industries, in wastewater and water resources. Rhodamine B is widely used in the dyeing of paints, plastics, textiles, and other fabrics, as well as biological products. It is highly persistent, toxic, and carcinogenic to organisms and humans when directly released into the water supply. To avoid this hazard, several studies have been conducted in an attempt to remove Rhodamine B from wastewater. Metal oxide semiconducting materials have gained great interest because of their ability to decompose organic pollutants from wastewater. TiO₂ is one of the most effective photocatalysts with a broad range of applications. Several attempts have been made to improve its photocatalytic activity. Accordingly, we have prepared in this work a series of cerium (Ce) and samarium (Sm) co-doped TiO₂ nanoparticles (x = 0.00, 0.25, 0.50, 1.00, and 2.00%) using a sol–gel auto-combustion approach. The influence of Ce–Sm concentrations on the structural, morphology, electronic, and optical properties, as well as the photocatalytic activity, was investigated. Structure and elemental mapping analyses proved the presence of Ce and Sm in the compositions as well as the development of the TiO₂ anatase phase with a tetragonal structure and crystallite size of 15.1–17.8 nm. Morphological observations confirmed the creation of spherical nanoparticles (NPs). The examination of the electronic structure properties using density functional theory (DFT) calculations and of the optical properties using a UV/Vis diffuse spectrophotometer showed a reduction in the bandgap energy upon Ce–Sm co-doping. The photocatalytic activity of the synthesized products was assessed on the degradation of Rhodamine B dye, and it was found that all Ce–Sm co-doped TiO₂ nanoparticles have better photocatalytic activities than pristine TiO₂ nanoparticles. Among all of the prepared nanoparticles, the sample with x = 0.50% demonstrated the best photocatalytic activity, with a degradation efficiency of 98% within 30 min and a reaction rate constant of about 0.0616 min⁻¹. h⁺ and •O₂⁻ were determined to be the most important active species in the photocatalytic degradation process. Besides the high photocatalytic degradation efficiency, these photocatalysts are highly stable and could be easily recovered and reused, which indicates their potential for practical applications in the future.