Advances in wireless communication protocols and networking toward support of the next generation of mobile and radio broadband technologies have contributed to a strong competition among various telecommunication standards in particular Long Term Evolution (LTE) and Mobile Worldwide Interoperability for Microwave Access (WiMAX). In this paper, we provide an in-depth comparison analysis of LTE and Mobile WiMAX at the physical (PHY) layer by studying the most similar PHY configuration scenarios for these two technologies. Our study includes a throughput analysis of downlink (DL) and uplink (UL) transmissions in time division duplex with the least overhead possible and different antenna schemes as well as modulation and code rates. This study also performs an overhead analysis in both protocols to provide a more in-depth understanding of the PHY layer capacity in various PHY layer configurations. Our simulation results generally show higher performance for LTE in both DL and UL transmission with 7 Mbps in DL and 5 Mbps in UL, when using one antenna port. However, by increasing the number of antennas for multiple-input/multiple-output configurations, the results illustrate a reduction in the performance of LTE compared to Mobile WiMAX. This arises from the increase in reference signal overhead in LTE from 4.7% in single-input/single-output (SISO) to 14.28% in 4 4 multiple-input/multiple-output (MIMO).