Flyhalf Caleb Muntz has scored 19 points as Fiji pulled off their first ever win in Wales, triumphing 24-19 at the Principality Stadium to consign their hosts to a record-equalling 10th straight Test defeat.
With Australia visiting Cardiff next Sunday (Monday AEDT), Wales now face the prospect of plunging to their worst ever record run should they lose 11 in a row.
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Muntz scored a superb individual try, which he converted, and put over four penalties for Fiji, who also scored a try through Josua Tuisova in Sunday's (Monday AEDT) clash.
Wales, who made a promising start to the test, scored through new cap Blair Murray, substitute Ellis Bevan and a penalty try with a single conversion from Gareth Anscombe on his long-awaited return to the side.
Murray, who was preferred to Rio Dyer in the Wales line-up on the left wing, justified coach Warren Gatland's faith with a sprint to the line to score a first try in the eighth minute.
Wales went over again in the 15th minute but Cameron Winnett's effort was chalked off after a dangerous clear out from Tommy Reffell in the build-up that earned the loose forward a yellow card.
Despite the disadvantage, Wales were awarded a penalty try four minutes later when Elia Canakaivata tried to pull down their driving maul, earning himself a 10-minute stay in the sin bin.
Fiji's woes were extended in the 21st minute when key winger Semi Radradra was cautioned, upgraded soon after to red, for a high hit on Winnett.
Radradra was sent off as World Rugby trialled a new red-card protocol, enabling Fiji to bring on a player after 20 minutes had passed.
Despite being down to 13, Fiji scored with a break from Muntz, who cut through the middle and accelerated away from the defenders for a brilliant 24th-minute individual effort that reduced the home lead to 14-10.
Two minutes into the second half, Muntz reduced Wales' lead to a single point when putting over a penalty, and then gave Fiji a 16-14 lead with another successful kick in the 49th minute.
Tuisova powered over for Fiji's second try on the hour mark, as a box-kick set up a powerful attack at the Welsh line and silenced the home crowd.
Substitute Jac Morgan, making a first appearance since last year's World Cup, helped to set up Wales's third try five minutes later with a carry that stretched the visiting defence and once the ball went down the line allowed Bevan to go over and reduce Fiji's lead to 21-19.
But it was the Pacific islanders who finished stronger, botching a chance for a third try with an errant pass six minutes from the end.
They had, however, a penalty advantage in the build-up and Muntz put over the close-in kick to leave Wales scrambling unsuccessfully in the closing stages to try to snatch the win, with Ryan Elias spilling the ball in their last attack.
Wales's last victory was a 43-19 triumph over Georgia at last year's World Cup, the game after they had also thrashed Australia.
Since then, they've been eliminated from the tournament by Argentina, suffered a Six Nations whitewash and mid-year losses to South Africa and twice to Australia.