Hamer-Webb, who left Cardiff for Leicester for the beginning of the 2025-26 season, makes his first start after his maiden Six Nations call-up.
The former Bath wing played age-grade rugby for England, but qualifies for Wales through his mother.
The 25-year-old will become the 1,221st men’s international when he runs out at Principality Stadium this weekend.
Scarlets wing Mee drops out, while Cardiff’s Josh Adams keeps his place having started the defeats against England and France.
“Gabe has impressed me in the way he’s attacked training, the way he’s adapted and the way he’s settled into the squad,” said Tandy.
“His training efforts have been outstanding.
“When you dig into his background at Leicester, even when he wasn’t in the team, everyone said he was an amazing team player.
“He also kept pushing, he never gave up and then when he had his Leicester opportunity he took it with two hands.
“Now this opportunity has come up and it’s thoroughly deserved.”
Costelow, 25, last played for Wales when he started the 24-19 defeat against Japan in Kitakyushu in July 2025.
Ospreys fly-half Edwards has started the past seven matches in the Wales number 10 role and Harlequins half-back Jarrod Evans has been used as a regular replacement.
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