Jurgen Klinsmann's men were rocked when Oalex Anderson put the Caribbean visitors ahead in the fifth minute at the Busch Stadium in St. Louis, Missouri.
But Bobby Wood equalized six minutes later and the United States cruised from there, with two goals from Jozy Altidore to go with goals from Fabian Johnson, Geoff Cameron and Gyasi Zardes.
The United States came into the match off of a Gold Cup flop on home soil and a defeat by Mexico in a crunch playoff for a place in the 2017 Confederations Cup in Russia.
So it was especially nervewracking for the crowd to see St. Vincent take a quick lead after Anderson seized upon a long ball over the top of the American defense. He cut and fired it past US keeper Brad Guzan.
Wood responded six minutes later, heading a ball from DeAndre Yedlin past St. Vincent goalkeeper Winslow McDowall.
Johnson extended the lead in the 29th when his free kick deflected off the wall and into McDowall's net.
Just two minutes later Altidore made it 3-1. Alone at the far post he headed into an open net after Jermaine Jones had nodded on a corner kick.
With the US playing aggressively and dominating possession, Cameron headed in a corner in the 51st.
Zardes made it 5-1 in the 58th and Altidore wrapped up the scoring with his second in the 74th, firing a left-footed blast from inside the area that shot off a defender and into the net.
It was just the start to qualifying that the US needed, and they will try to maintain the momentum when they visit Trinidad and Tobago on Tuesday.
The match was played before 43,433 fans at the home of baseball's St. Louis Cardinals.
A moment of silence was observed before kickoff to pay respect to the victims of terror attacks in Paris earlier Friday.