The present work reports an experimental investigation of a zero- and single-extraction humidification-dehumidification (HDH) desalination system. While rich thermodynamic modeling of mass extraction/injection-based HDH systems exists in the literature, studies providing design guidelines are lacking. This work aims to elucidate practical design aspects experimentally and report a simple tool for component and system sizing based on the understanding gained from experiments. The effect of the operating parameters such as airflow rates, water flow rates, extraction airflow ratio, top cycle temperature, and salinity on the energy efficiency and yield of the HDH desalination system with and without mass extraction/injection was experimentally examined. It was observed that there is an optimal airflow rate and water flow rate for a zero extraction HDH desalination system at a given top-and-bottom-cycle temperature. The design of mass extraction/injection in advanced HDH cycles involves identifying two key elements of design: (a) location of extraction and (b) amount of airflow extraction/injection. The effect of the airflow extraction location and ratio on the thermal energy efficiency of the single extraction HDH system is reported for different air flow rate conditions. The maximum gained-output ratio for zero- and single-extraction HDH systems was 1.74 and 1.86, respectively. A simple effectiveness-based mathematical model for a single-extraction HDH system is reported that enables component and system sizing.