This study compares two numerical strategies for modeling flow and heat transfer through mini- and microchannel heatsinks, the unit cell approximation, and the full 3D model, with the objective of validating the former approach. Conjugate heat transfer and laminar flow through a 2 × 2 cm2 copper–water heatsink are modeled using the finite element package COMSOL Multiphysics 5.0. Parametric studies showed that as the heatsink channels’ widths were reduced, and the total number of channels increased, temperature and pressure predictions from both models converged to similar values. Relative differences as low as 5.4% and 1.6% were attained at a channel width of 0.25 mm for maximum wall temperature and channel pressure drop, respectively. Due to its computational efficiency and tendency to conservatively overpredict temperatures relative to the full 3D method, the unit cell approximation is recommended for parametric design of heatsinks with channels’ widths smaller than 0.5 mm, although this condition only holds for the given heatsink design. The unit cell method is then used to design an optimal heatsink for server liquid cooling applications. The heatsink has been fabricated and tested experimentally, and its thermal performance is compared with numerical predictions. The unit cell method underestimated the maximum wall temperature relative to experimental results by 3.0–14.5% as the flowrate rose from 0.3 to 1.5 gal/min (1.1–5.7 l/min).