Ni-YSZ anode of solid oxide fuel cells (SOFCs) with three different compositions are examined and compared through electrochemical measurement, microstructural analysis, and numerical simulation. Three-dimensional (3D) microstructure of the porous anodes is directly observed using focused ion beam and scanning electron microscope (FIB-SEM), and microstructural parameters such as phase connectivity and three-phase boundary (TPB) density are quantified to correlate the microstructure to the performance. 3D numerical simulation using the obtained microstructure is conducted considering the various transport phenomena and the electrochemical reaction in the anodes to predict their overall electrochemical performance. The performance of the Ni:YSZ = 30:70 anode is measured significantly lower than those of the Ni:YSZ = 50:50 and 70:30 anodes, which is attributed to the elongation of the ionic transport pathways. The poor connectivity of the Ni phase in the Ni:YSZ = 30:70 anode shifts the electrochemically active region far from the anode–electrolyte interface, resulting in higher Ohmic loss. The amount and distribution of the effective TPB associated with the phase connectivity are essentially important to explain the anode performance. The 3D numerical simulation qualitatively reproduces the anode performance and gives detailed information about the internal states of the anodes such as the distribution of the charge-transfer current.