A limited number of herbicides and sites of action are registered for use in sugarcane in Louisiana. Repeated use of the same sites of action can lead to the evolution of herbicide resistance in weeds. Therefore, it is critical to evaluate additional sites of action to provide growers with options for rotating herbicides to reduce the risk of resistance. Topramezone, indaziflam, and a formulation including mesotrione, bicyclopyrone, atrazine, and S-metolachlor, along with more common herbicide applications (pendimethalin, and metribuzin, clomazone, and diuron), were evaluated in the spring for injury to sugarcane, weed control, sugarcane yield, and sugar yield. Of these treatments, clomazone applied with diuron was the only herbicide combination to consistently injure the crop, with injury estimates ranging from 11 to 36%, which frequently resulted in reduced sugar yield with losses between 2.3% to 24.1% of the non-treated control. In most treatments, an increase in itchgrass counts was observed between harvests, indicating that additional control strategies will be needed in fields infested with this weed. However, topramezone alone and with triclopyr was well tolerated by sugarcane, with injuries ranging from 0 to 11% two weeks after treatment. Indaziflam and combined application of mesotrione, bicyclopyrone, atrazine, and S-metolachlor injury was at or under 10% two weeks after treatment. The tolerance of sugarcane for these herbicides suggests that they can be incorporated into weed management strategies in sugarcane. These herbicides would increase the sites of action available to be applied in sugarcane and help mitigate the risk of herbicide-resistant weeds.