South Carolina state highway SC 133 is a Pickens County road that runs about 29 miles from a T-intersection on the Cherokee Foothills Scenic Highway, SC 11, in the north to the intersection with the Old Greenville Highway (SC 93) on the edge of Bowman Field on the Clemson University campus on the south end.
Following primarily a south-southeast alignment, SC 133 serpentines south as Crowe Creek Road from the Keowee Toxaway State Park on the south side of a branch of Lake Keowee, before heading briefly eastward sharing the alignment of Shady Grove Road as far as the Shady Grove Baptist Church. SC 133 then diverges southward, still carrying the Crowe Creek Road name. It crosses another arm of Lake Keowee, and further south, has a junction with Mile Creek Road near Mile Creek Baptist Church.
Just after passing Ile Creek Lake, Keowee Baptist Church Road intersects from the west. The Crowe Creek Road name ends at the intersection with the Walhalla Highway (SC 183) at Durham's Convenience Store. Continuing south of SC 183, SC 133 becomes Mt. Olivet Road for the next few miles into the Town of Six Mile. In the town, SC 133 shares an alignment with SC 187 and is named North and South Main Street, splitting where 6 Mile Road heads east. SC 187 heads southeast as the Norris Highway, while SC 133 continues southward as South Main Street. Outside of town, it becomes known as both the Six Mile Highway and the Old Six Mile Highway, traveling several miles until it passes D. W. Daniel High School.
Just east of the high school, SC 133 diverges further south while State Road S-39-15 heads east towards Central as Madden Bridge Road. SC 133 intersects R. C. Edwards School Road before crossing four arms of Lake Hartwell on its way into the old Calhoun district of Clemson, passing under the alignment of the Norfolk Southern railway line. The Six Mile Highway gives over to College Avenue in the university community, and serves as Clemson's main street to the campus.