The game against Surrey began badly for Durham, who had both openers bowled inside the first five overs – Suzie Bates and Mady Villiers dismissed by Ryana MacDonald-Gay.
From 29-3, Hollie Armitage led a revival, adding 40 with Bess Heath (27) and 38 with Mia Rogers, and although she went to 50 off 49 balls in the last over and Katherine Fraser hit the final ball of the innings for six, their score did not look enough.
So it proved as Wyatt-Hodge and Bryony Smith matched each other shot for shot in bringing up a 50 partnership in the fourth over.
Wyatt-Hodge launched Katie Levick over mid-wicket for a maximum, the first of two sixes in her innings to go with 11 fours, but the stand came to an end on 94 when Smith was caught in the deep off Phoebe Turner for 44 from 28 balls.
Replacement Kira Chathli opened her account with a six and made an unbeaten 19 from 13 before Wyatt-Hodge ended the game by cutting Bates to the point boundary.
“It definitely is a big win. We bowled and fielded really well as a team and then Danni and Bry smashed it and got us over the line,” said MacDonald-Gay.
“They are very good players who work really well together because they are different and they score in different areas, so it must be really tricky to bowl to them as a pair.”