Lauren Bell took three wickets for Southern Brave as they beat Manchester Originals by six wickets at Emirates Old Trafford.
A disastrous start saw the hosts reduced to 39-5 after 41 balls, starting when Bell (3-28) bowled Kathryn Bryce with the third delivery of the match before dismissing Amelia Kerr for 14.
Mady Villiers (2-19) also claimed two early scalps in skipper Beth Mooney (1) and Eve Jones (7), and the wickets continued to tumble as Deandra Dottin (8) and Alice Monaghan (5) fell for single figures before Fi Morris (1) was caught and bowled by Bell for her third wicket.
Sophie Ecclestone (3) was bowled by Georgia Adams (1-8), but Seren Smale (40no) continued to rally for the Originals - becoming only the second player of their innings to reach double figures - with an unbeaten 40 from 34 balls as her side eventually closed on 95-8.
Although Maia Bouchier (6) fell early in Brave's response, Laura Wolvaardt (42no) and Danni Wyatt-Hodge (32) put on 48 runs from 36 deliveries before the latter was bowled by England team-mate Ecclestone (1-24).
New batter Sophie Devine was dismissed for a duck by Danielle Gregory (1-11) and Ecclestone caught Freya Kemp (7) off Kerr, but Wolvaardt safely steered Southern Brave to a comfortable victory.
"It's great to get a first win on the board. Great to get a good start in tournament cricket," Player of the Match, Bell, told Your Site Cricket.
"The girls got stuck in. It was a tricky pitch, but we have a great batting line-up that did the job.
"We talked about being confident and having fun and backing our strengths. We want to go out and have fun every game."
Southern Brave will play Birmingham Phoenix on Sunday, August 10, at Utilita Bowl (11am), with Manchester Originals facing Oval Invincibles on Saturday, August 9, at The Kia Oval (11am).
Thursday's Hundred double header is between Northern Superchargers and Welsh Fire at Headingley (women's match at 3pm, men's at 6.30pm)
Watch every match from The Hundred live on Your Site Cricket up to and including the finals at Lord's on Sunday August 31.