Batting first after winning the toss, England were limited to 103 for seven from their 20 overs with captain Sarah Taylor top-scoring with 27 as Alisa Mohammed, Shanel Daley and Shemaine Campbelle each took two wickets apiece for the tourists.
However, while that total was significantly less than the 150 for three England managed in the second match, it proved enough to defeat West Indies and seal the five-match series.
Spinner Holly Colvin again impressed with figures of three for 13 off her four overs while seamer Arran Brindle took three for 16 as West Indies were bowled out for 93 in the final over.
Deandra Dottin was one of only two Windies batters to get into double figures but she kept her side in with a chance of victory until she fell in the penultimate over following a 17-ball 24 that included two fours and a six.
Player of the match Arran Brindle said: “We hoped to get the best out of the track batting first so we were pleased to win the toss. We looked to hit the big corners and run twos to get the runs on the board and it paid off.
"We knew we were always in the game, we just had to bowl well and we did that. I was pleased to contribute but all the bowlers bowled well today, wickets are great but economy is the biggest thing in Twenty2 cricket.
“Every game is massive for this team; we want to win every game so just because we are three games up in the series doesn’t mean we are going to take our foot off the gas.
“I’m really looking forward to the game at my home ground of Hove on Saturday and hope people come down to support us.”