With the significant increase in use and application of graphene and the frequent presence of sulfonamides (SAs) in water environments, their interactions have attracted extensive attention. In this study, adsorption of two selected SAs (sulfapyridine and sulfathiazole) by two reduced graphene oxides (rGO1 and rGO2) was examined as affected by pH and dissolved organic matter (DOM). Adsorption of SAs by rGOs was highly pH-dependent, and adsorption affinity of different SAs species followed the order of SA0 > SA+ > SA−. The contribution of SA0 to the overall adsorption was greater than its species fraction, implying the importance of the neutral species to adsorption. SAs adsorption isotherms at three selected pHs were in the order of pH 5.0 > pH 1.0 > pH 11.0, which was in accordance with the variation of site energy distribution analysis. Hydrophobic interaction, π–π EDA interaction and electrostatic interaction were the main mechanisms responsible for SAs adsorption by rGOs. Three representative natural DOMs including humic acid (HA), bovine serum albumin (BSA), and sodium alginate together with sodium dodecylbenzenesulfonate (SDBS) as a synthetic DOM were used to investigate their effect on SAs adsorption. The inhibition impact of DOM on SAs adsorption was lower for rGOs compared with carbon nanotubes and graphite, which might be attributed to the higher oxygen contents of rGOs. Also, the suppression effect of DOM generally followed an order of SDBS > HA ≥ BSA > alginate, indicating the importance role of DOM compositions. These results should be important for assessing the fate and transport of graphene and antibiotics in the environment.