The seventh-seeded Anderson, the first South African to win this 20-year-old tournament, is now 2-1 in career finals, having won his first title at the now defunct 2011 Johannesburg tournament.
"It's fantastic," said Anderson, who went to the University of Illinois and lives in the Chicago area where his wife, Kelsey, grew up. "First title in the United States which is great. Apart from South Africa this is my second home. Winning one in the United States is especially exciting."
The 36th-ranked Anderson -- he'll move up to around No. 30 in the next rankings -- gained a lot of attention here this week as he beat the two American favorites -- Andy Roddick in the quarterfinals and John Isner in the semis.
The 173rd-ranked Matosevic had the best week of his career despite losing in his first career. The 26-year-old, who came in with a 3-15 record on the ATP Tour, had never before won consecutive matches.
The final loss ended Matosevic's overall winning streak of 12 matches. He won all five matches while winning the Caloundra Challenger in Australia, then won three qualifying and four main draw matches at Delray Beach.
"I'm pretty tired," Matosevic said. "I woke up feeling good even though I only had four hours sleep, but when I stepped out there I felt worse than I thought. I think it was a culmination of the whole week. My energy levels were pretty low. But Kevin did what he had to do out there, making a few more balls and he served great today."
Matosevic will move up to around No. 127 in this coming week's rankings, which will be a career best. His previous highest ranking was 131st last March 7.
The first five games of the match ended in service breaks before Anderson settled down to hold serve to take a 4-2 lead. He held onto the edge to close out the opening set.
"I thought I got off to a good start with that break, but I just think a little bit nervous for me," Anderson said. "I don't know how he was feeling. I felt he was making a few more serves than me and I was making some more baseline exchanges.
"I just had to find my rhythm. But after that second break (in the fourth game of the first set) I never faced another break point."
Both players picked up their game in the second set, but Matosevic kept having to fight his way out of trouble.
While serving the first game he saved on break point. In the third game he saved three break points. In the seventh game he saved three more break points. In the 11th game he saved another break point.
In the tiebreaker, Matosevic surrendered his first three serves to find himself behind 4-0. On Anderson's second match point -- both on Matosevic serves -- the Australian netted a forehand to lose the match.