In view of the unique oceanographic conditions combined with human pressure, we assessed the ecological status of macrobenthos from the entire Saudi waters (including open waters and inner bays) of the Gulf in 2013. A total of 328 macrobenthic species (228 polychaete species, 47 crustacean species, 46 mollusc species, and seven species belonging to other taxa) was recorded from the study area. Species richness, species diversity, and density had an overall average ±SE of 34 ± 2.0, 4.02 ± 0.1 and 1,373 ± 160 ind. m−2, respectively. As per the results of AZTI’s Marine Biotic Index (AMBI), in open waters, 10% of stations belonged to undisturbed and the remaining 90% belonged to slightly disturbed categories, while in sheltered inner bays, 95% of the stations belonged to slightly disturbed and the remaining 5% belonged to moderately disturbed categories. According to Multivariate AMBI (M-AMBI), 4% of the stations showed high status, 74% good status, 23% moderate status and 1% poor status in open waters. In inner bays, 2% of the stations showed high status, 73% good status, 14% moderate status and 4% poor status. The open waters, where extensive industrial activities take place, are not under major stress, which might be due to the implementation of appropriate mitigation measures during the construction and operation of the offshore facilities and the natural dispersal of potential pollutants. The stressed conditions on benthos in inner bays might be due to coastal discharges besides extreme oceanographic conditions, including the poor water flushing rates, which increase the exposure to pollutants.