Winston made good on 19-of-21 attempts for 277 yards in just over two quarters play for the Seminoles (10-0, 8-0 ACC), who have games with Idaho and rival Florida remaining in their quest for an undefeated season.
James Wilder Jr. scored twice on three carries, finishing with 52 yards.
Karlos Williams picked up 78 yards on four carries, while Kermit Whitfield and Devonta Freeman also each ran for an FSU touchdown.
The Orange (5-5, 3-3) struggled as Terrel Hunt was sacked three times. He completed 10-of-18 passes for just 75 yards.