Runner-up here in 2002, the American 11th seed overcame a second-set fightback to advance in sweltering conditions at Roland Garros.
After building a 4-0 lead in the third set, Williams allowed Zuluaga to fight back before finally winning through.
The former world number one will face either Shinobu Asagoe or Sesil Karatantcheva next.
Results from the Women's Singles Round 2 matches:
11-Venus Williams (United States) beat Fabiola Zuluaga (Colombia) 6-3 3-6 6-3
Emilie Loit (France) beat 27-Amy Frazier (United States) 6-4 6-4
Akiko Morigami (Japan) beat 31-Karolina Sprem (Croatia) 7-5 6-3