Poland's Radwanska rolled to a comfortable 6-4, 6-2 victory over the American in just 81 minutes as she claimed her 14th career singles title.
"I am very, very happy," said Radwanska, who earned $467,000 for the win. "Everything was working for me today."
The 25-year-old's last win was in Seoul in September. She reached the final at Indian Wells earlier this year, losing to Italian Flavia Pennetta.
Radwanska fired three aces, had two double faults and won 65 percent of her first serves in the hardcourt match on centre court.
The 2012 Wimbledon runner-up dropped the opening game of the first set, but then ran off four straight games to take control. Williams broke back and drew within 4-3 only to see Radwanska win the set 6-4.
The former world number two then broke Williams to open the second set, but the Florida resident got back into it with a fourth-game break to even the set at 2-2. Radwanska broke back in the fifth game to regain control.
"I was just trying to use my chances," Radwanska said. "Whenever I could really go for it, that's what I tried to do.
"On a couple of her serves I really had no chance. But if I had any chance, I took it and that's why I could break her."
Radwanska has now won 11 of her 14 crowns on hardcourt.
"I had an amazing week," she said. "I was playing much better with each match. I didn't start that well from my first match but every match was much better. That is why I am sitting right here."
Williams, who beat her sister Serena in the semi-finals, had six double faults and won just 26 percent of her second serves in the loss.
The 34-year-old American had played three straight three-set matches.
"I fell a little short. I didn't have as much to give as I would have liked," Williams said.
"It has been a really long week. I would love to play six matches again next week but it is a lot.
"I ran out of energy because I was winning too many matches. I haven't had that problem in a long time."
Radwanska improved to 4-5 career against Williams, who was seeking her second title of 2014.
Williams collected $227,000 in prize money to go over $30 million in career earnings. She will also improve her ranking from the current world number 26.
- Sports & Recreation
- Agnieszka Radwanska
- Venus Williams