The development of fluridone resistance by hydrilla has significantly impacted hydrilla management, and research is ongoing to develop alternate herbicides for effective hydrilla control. We determined the potential cross-resistance in fluridone-resistant hydrilla to other bleaching herbicides norflurazon, mesotrione, and topramezone-methyl. Phytoene, β-carotene, and chlorophyll contents as a function of hydrilla biotype and herbicide treatment were evaluated. Hydrilla shoot tips were collected from fluridone-susceptible (S) and -resistant (R) biotypes and exposed to 5, 25, 50, 75, and 100 µg L−1 of herbicide. The susceptible biotype showed an increase in phytoene and a decrease in β-carotene and chlorophyll contents when treated with 5 µg L−1 fluridone, whereas higher doses of fluridone were required to affect these pigments in the resistant biotype. There was no difference in response by S and R biotypes to mesotrione and topramezone-methyl, with both biotypes showing significant affects on pigment contents at 5 µg L−1. Higher doses of norflurazon were required to affect these pigments in the R compared to the S biotype. The S biotype had EC50 values of 11.7, 12.2, and 4.7 µg L−1, whereas the R biotype had EC50 values of 56.6, 41.1, and 41.7 µg L−1 fluridone for phytoene, β-carotene, and chlorophyll contents, respectively. There was no difference in EC50 for phytoene, β-carotene, and chlorophyll values between the hydrilla biotypes for mesotrione and topramezone-methyl herbicides. In fluridone-susceptible and -resistant hydrilla biotypes, EC50 values for phytoene, β-carotene, and chlorophyll were 12.4 to 11.8, 10.2 to 13.2, and 3.1 to 4.6 µg L−1 mesotrione and 12.6 to 13.5, 13.3 to 11.9, and 4.6 to 5.7 µg L−1 topramezone-methyl, respectively. For norflurazon, S and R biotypes had EC50 values of 33.1, 45.4, and 40.6 µg L−1 and 84.6, 81.0, and 92.7 µg L−1 for phytoene, β-carotene, and chlorophyll, respectively. These studies confirmed negative cross-resistance of fluridone-resistant hydrilla to mesotrione and topramezone-methyl and a positive cross-resistance to norflurazon.