Brandon Pye, fresh off a career high 21 in his last outing, added 16 points for the Islanders (8-8, 3-1 Southland Conference), who have now won four of their last five overall.
The Islanders went on a 12-2 run midway through the second half, capped off on a layup by Ehab Amin, which put them ahead for good. A Sam McBeath bucket for the Colonels with 1:27 remaining trimmed the lead to two, but Pye's 3-pointer 17 seconds later iced it.
McBeath scored 18 points and added 10 boards to lead Nicholls St (4-10, 1-3).
The game was the fourth consecutive win for the Texas A&M-CC over Nicholls St, and lifts its record to 8-3 against them.