RaShawn Stores had 12 points, while Emmy Andujar added 11 and a team-high seven rebounds.
Manhattan (3-5, 1-1) built a 22-9 lead 10:30 into the first half behind five consecutive layups—four by Brown—and a 3-pointer from Andujar.
O.D. Anosike’s layup cut the deficit to two, 38-36, in the second half but Manhattan outscored Siena 12-2 over the next 5 minutes to push its lead to 50-38.
Manhattan, which hit six 3s in the second half, held the Saints to two field goals over the final 6 1/2 minutes to pull away.
Rakeem Brookins scored 19 for Siena (2-9, 1-1), which held a 36-35 rebounding edge but got only four points off the bench, compared to 34 for Manhattan.