Established as a new primary routing in 1930 or 1931, originally ran from SC 9, near Richburg, to the York County line. In 1933, it was extended north to US 21. In 1940, it was extended south to its current southern terminus with SC 22 (today SC 200). Between 1949-50, it was briefly truncated south at SC 97. Between 1974-79, it was extended north to SC 5. In 1992, it was extended again to its current northern terminus with SC 161/SC 274.
In 2010, SC 901 was widen to four-lane from Interstate 77 to SC 121, thanks to the "Pennies for Progress" project fund.