Heat exchangers with mini- and micro-channel components are capable of high energy exchange due to their incumbent large surface area to volume ratio. Concurrently, recent advances in additive manufacturing simplify the creation of metallic minichannels that incorporate turbulators for heat transfer enhancement. As part of the development of a minichannel heat exchanger with turbulators, this study analyzes the three-dimensional conjugate heat transfer and laminar flow in a minichannel heat exchanger equipped with rectangular winglet vortex generators (VGs) through numerical simulation. The minichannels have a hydraulic diameter of 2.86 mm and are assumed to be made from aluminum alloy AlSi10Mg. This material is one of the popular alloys in the additive manufacturing industry (three-dimensional (3D) printing) because of its light weight and beneficial mechanical and thermal properties. The working fluid is distilled water with temperature-dependent thermal properties. The minichannel is heated by a constant heat flux of 5 W cm−2 and the Reynolds number is varied from 230 to 950. The simulations are performed using the COMSOL® platform, which solves the governing mass, momentum, and energy equations based on the finite element method. The effect of the VG design parameters, which include VG angle of attack, height, length, thickness, longitudinal pitch, and distance from the sidewalls, is investigated. It is found that the generation of three-dimensional vortices caused by the presence of the vortex generators can notably boost the convective heat transfer, at the cost of increased pressure drop, potentially reducing the heat exchanger size for a given heat duty. A sensitivity analysis indicates that the angle of attack, VG height, VG length, and longitudinal pitch have the most significant effects on the heat transfer and flow friction characteristics. In contrast, the VG thickness and distance from the sidewalls only had minor influences on the heat exchanger performance over the studied range of design parameters.