Waste-derived organics introduced to soils along with pharmaceutical active compounds (PhAC) are a crude mixture of compounds occurring in various size and polarity fractions. They affect the sorption of PhACs to soil; however, the relevant knowledge is still insufficient. The effects of different size and polarity fractions of manure-derived mobile organic matter (<63 µm) on the sorption of sulfadiazine, caffeine and atenolol to five topsoils were investigated. Mobilization of the PhACs was strongest in the presence of dissolved organic matter (mDOM, <0.45 µm), with a reduction of Kd of sulfadiazine, caffeine and atenolol by mean factors of 0.66, 0.57 and 0.41, respectively. The mobilizing effects of colloidal organic matter (0.45–10 µm) were slightly smaller. Fine particulate organic matter (10–63 µm) reduced the sorption of the PhACs in slightly acidic soils (pH 6.0), but increased it in strongly acidic soil (pH 4.3). Furthermore, hydrophobic (HO-mDOM) and hydrophilic (HI-mDOM) fractions of mDOM reduced the sorption capacity but increased the sorption nonlinearity of PhACs in soils. Effects of HO-mDOM and HI-mDOM were PhAC specific. It is suggested to consider the varying impacts of mobile fractions in animal manure and/or treated wastewater in evaluating the fate and environmental relevance of associated PhACs.