Three-dimensional (3D) printing, known as additive manufacturing, provides new opportunities for the design and fabrication of highly efficient industrial components. Given the widespread use of this technique by industries, 3D printing is no longer limited to building prototypes. Instead, small-to-medium scale production units focus on reducing the cost associated with each part. Among the various industrial components that can be developed with this manufacturing technology are heat transfer components such as heat exchangers. To this end, this study investigated the heat transfer characteristics of minichannel-based heat exchangers embedded with longitudinal vortex generators, both experimentally and numerically. Three enhanced prototypes with different vortex generator design parameters and a smooth channel as a reference case were printed with an aluminum alloy (AlSi10Mg) using direct metal laser sintering (DMLS). The rectangular minichannel had a hydraulic diameter of 2.86 mm. Distilled water was used as the test fluid, and the Reynolds number varied from 170 to 1380 (i.e., laminar flow). Prototypes were tested under two different constant heat fluxes of 15 kW m−2 and 30 kW m−2. The experimental results were verified with a commercial simulation tool, Comsol Multiphysics®, using the 3D conjugate heat transfer model. In the case of the smooth channel, the experimental results were also compared with well-known correlations in the field. The results showed that 95% and 79% of the experimental data were within 10% of the numerical simulation results and the values from the existing correlations, respectively. For the channel enhanced with the vortex generators, the numerical predictions agreed well with the experimental results. It was determined that the vortex generators can enhance the convective heat transfer up to three times with the designed parameter. The findings from this research underline the potential of additive manufacturing in the development of more sophisticated minichannel heat exchangers.