Ruminants ingest large quantities of clay minerals along with inorganic soil constituents in roughages. The layered structure of clay minerals, however, may adsorb cations and may, thus, interfere with the ruminants' supply of essential trace metals, such as Zn, Mn, Cu, and Fe. As quantitative knowledge about interactions between clay ingestion and essential trace metal metabolism are largely lacking, this in vitro study focussed on the effect of clay on the solubility of dietary Zn and other bivalent trace metals in the digestive tract of ruminants. Therefore, buffered rumen fluid was used for the simulation of ruminal conditions (RC), acidified rumen fluid (pH 2) was used for abomasal conditions (AC), and duodenal chyme was used for duodenal conditions (DC). These media were added with gradient levels of zinc and incubated at 39 °C for 24 h in the absence or presence of clay minerals. Soluble Zn, Cu, Mn, and Fe were derived by centrifugation (10,000× g ) of incubated media, and the supernatants were analysed. Clay depressed the solubility of added Zn in ruminal (65.3% vs. 16.5%), abomasal (97.7% vs. 33.7%), and duodenal conditions (41.3% vs. 21.1%), the results of which were statistically significant ( p < 0.001). Moreover, clay reduced dissolved Cu (µg/mL) (RC: 0.13 vs. 0.10; AC: 0.16 vs. 0.13; DC: 0.10 vs. 0.08) and Mn (µg/mL) (RC: 3.00 vs. 1.80; AC: 5.53 vs. 4.80; DC: 3.18 vs. 1.77) ( p < 0.05 in all cases). The presence of clay minerals increased the concentrations of solubilised Fe (µg/mL) in abomasal (1.80 vs. 2.86, p < 0.05) and duodenal conditions (1.76 vs. 2.67; p < 0.05). In total, the present in vitro study demonstrates the potential of clay minerals ingested with ruminant feeds for depressing the solubility of dietary Zn, as well as the depression of dietary Cu and Mn along the passage of the digesta from the rumen until the duodenum. Additionally, clay minerals may release Fe into the digesta.