7α-Hydroxypregnenolone is an endogenous neuroactive steroid that stimulates locomotor activity. A synthesis of 7α-hydroxypregnenolone from pregnenolone, which takes advantage of an orthogonal protecting group strategy, is described. In detail, the C7-position was oxidized with CrO3 and 3,5-dimethylpyrazole to yield a 7-keto steroid intermediate. The resulting 7-ketone was stereoselectively reduced to the 7α-hydroxy group with lithium tri-sec-butylborohydride. In contrast, reduction of the same 7-ketone intermediate with NaBH4 resulted in primarily the 7β-hydroxy epimer. Furthermore, in an alternative route to the target compound, the 7α-hydroxy group was successfully incorporated by direct C–H allylic benzoyloxylation of pregnenolone-3-acetate with CuBr and tert-butyl peroxybenzoate followed by saponification. The disclosed syntheses to 7-oxygenated steroids are amenable to potentially obtain other biologically active sterols and steroids.