Tremain Paul was the first of five different scorers for St. Lucia in the 14th minute, which led 2-0 at halftime and added a pair of goals in the final three minutes - one of which came after Curacao was reduced to 10 men.
In the early game of the first-round Group 2 doubleheader at Beausejour Stadium, Cornelius Stewart scored in the 79th minutes - his third straight match with a goal - and gave St. Vincent the victory over Guyana.
The Golden Jaguars have lost nine of their last 10 since a 2-1 victory over Grenada in a February 21 friendly, with only by a 2-2 draw against El Salvador in World Cup qualifying on September 7.
Myron Samuel gave St. Vincent the lead in the 30th minute before Gregory Richardson equalized in the first minutes of first-half injury time. Richardson's goal was the first in nearly three full games for Guyana, which lost its previous two matches to Mexico and Costa Rica 12-0 in World Cup qualifying.
The victory was the fourth in six games for St. Vincent.
For St. Lucia, Magnam Valcin put St. Lucia ahead 2-0 a minute before halftime, and after Isenia Alexander tried to rally Curacao with a 48th-minute goal, Eden Charles restored the two-goal advantage in the 51st.
Tafari Charlemagne tacked on additional insurance in the 87th, and Kurt Frederick completed the scoring in the 92nd - but not before Delando Felipe drew his second yellow three minutes earlier.
The victory was the first for St. Lucia since 4-2 win over Aruba on July 12, 2011, to advance to the second round of World Cup qualifying.
Group 2 will resume on Tuesday with Curacao vs. Guyana, and St. Lucia vs. St. Vincent. The winner of Group 2 will advance to the second round and join Grenada, Haiti and French Guyana, while the runner-up also will advance, joining Cuba, Trinidad & Tobago and Suriname.