Because of their fuel flexibility, Solid Oxide Fuel Cells (SOFCs) are promising candidates to coach the energy transition. Yet, SOFC performance are markedly affected by fuel composition and operative parameters. In order to optimize SOFC operation and to provide a prompt regulation, reliable performance simulation tools are required. Given the high variability ascribed to the fuel in the wide range of SOFC applications and the high non-linearity of electrochemical systems, the implementation of artificial intelligence techniques, like Artificial Neural Networks (ANNs), is sound. In this paper, several network architectures based on a feedforward-backpropagation algorithm are proposed and trained on experimental data-set issued from tests on commercial NiYSZ/8YSZ/LSCF anode supported planar button cells. The best simulator obtained is a 3-hidden layer ANN (25/22/18 neurons per layer, hyperbolic tangent sigmoid as transfer function, obtained with a gradient descent with adaptive learning rate backpropagation). This shows high accuracy (RMS = 0.67% in the testing phase) and successful application in the forecast of SOFC polarization behaviour in two additional experiments (RMS in the order of 3% is scored, yet it is reduced to about 2% if only the typical operating current density range of real application is considered, from 300 to 500 mA·cm−2). Therefore, the neural tool is suitable for system simulation codes/software whether SOFC operating parameters agree with the input ranges (anode feeding composition 0–48%vol H2, 0–38%vol CO, 0–45%vol CH4, 9–32%vol CO2, 0–54%vol N2, specific equivalent hydrogen flow-rate per unit cell active area 10.8–23.6 mL·min−1·cm−2, current density 0–1300 mA·cm−2 and temperature 700–800 °C).