Objectives: The nucleic acid-binding cleft in HIV-1 reverse transcriptase (HIV-1 RT) is essential because of its interactions with the polymerase and RNase H active sites. Studying its binding sites for nucleoside reverse transcriptase inhibitors (NRTIs) is crucial for understanding how to effectively select drug compounds, properly administer drugs, and prevent drug resistance. Materials and Methods: We conducted docking studies using Molegro Visual Docker, and then we used SwissADME software to analyze the physicochemical properties and pharmacokinetics of the compounds. Results: The molecular docking results of the studied compounds with the HIV-1 reverse transcriptase model (6ASW) showed that zalcitabine has the highest ligand efficiency for the enzyme model. The binding sites of the studied compounds were investigated, revealing that all the compounds bind to sequences containing amino acids 34, Val 35, and Val 60, or connect to a binding site containing amino acids Val 90, Gln 91, Leu 92, Gln 161, Ser 162, Thr 165, and Gln 182 in the p66 subunit. Only Zidovudine binds to the sequence of amino acids Asp 110, Tyr 183, Asp 186, Lys 220, Gln 222, Met 230, and Gly 231, which are in the active site of the enzyme. Conclusions: We emphasize the crucial role of NRTIs' affinity for the enzyme in inhibiting HIV-1 reverse transcriptase. It is important to monitor and understand resistance mutations of the HIV-1 reverse transcriptase enzyme for effective drug administration strategies.