Management of sugarcane orange rust, caused by Puccinia kuehnii, currently relies on fungicide applications in Florida. Field experiments were conducted in 2016 and 2017 in Belle Glade, FL to evaluate the efficacy and application timing of fungicides on progress of disease severity and sugarcane yields. Two treatment programs of three fungicide applications each were applied to sugarcane cultivar CL85-1040 susceptible to orange rust. Each program was also started at three different initiation dates separated by one month, and the first treatment was initiated when rust severity reached 5–10% on the top visible dewlap (TVD) leaf. Program A consisted of two consecutive applications of fluxapyroxad + pyraclostrobin followed by an application of metconazole. Program B consisted of three consecutive applications of fluxapyroxad + pyraclostrobin, fluxapyroxad, and pyraclostrobin. For each program, the three fungicide applications were separated by one month each and control plots remained unsprayed. Percent leaf area affected by rust was recorded every two weeks on TVD leaf and leaf +2 (leaf immediately below TVD leaf). Fungicide treatment programs initiated at the beginning of orange rust epidemics resulted in highest reduction of disease severity (41–45%) and highest yield increase (26–33%) as compared to untreated control plants. These results suggested that the application of fungicides initiated through early epidemic season are required for best management of sugarcane orange rust.