The Australian, who left the PGA Tour for the controversial Saudi-backed tournament after becoming number two in the world - the highest-ranked player to join, closed with a three-under 69 for a three-shot victory at the Chicago Invitational.
The 29-year-old was briefly threatened in the third and final round at Rich Harvest Farms but he restored his lead with a birdie on the 17th to ensure neither Dustin Johnson nor Peter Uihlein could catch him.
Smith and the rest of the LIV golfers are not currently earning any world rankings points for their performances on the breakaway circuit, though it has applied for recognition.
Speaking after his win, Smith said he hoped the issue would be resolved soon.
"I suppose there's a lot on the line with the ranking points, getting into majors, stuff like that," he said.
Johnson and Uihlein tied for second after each made birdie on the par-5 18th hole. Johnson finished with 70 while his compatriot Uihlein finished with 69 - both earning 1,812,500 dollars (£1,589,417) from the 20-million-dollar purse (£17.5 million).
Johnson is the only player from the 48-man field to have finished in the top 10 at every LIV Golf event and he remains one of the most significant players to sign up.
The 38-year-old is a two-time major champion who was number one in the world longer than any player since Tiger Woods.
The next LIV Golf event is in three weeks in Bangkok.
The series does not return to America until the final team event at Trump Doral near Miami in October.
As well as Smith and Johnson, the Saudi-backed rebel tour has attracted Brooks Koepka and Bryson DeChambeau.