Hull were left still seeking their first away win of the Super League season after throwing away an early lead to suffer a dismal defeat.
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Widnes trailed 12-4 until just before half-time but hit back with two tries apiece from man of the match Paddy Flynn and Cameron Phelps.
Widnes made half a dozen changes after a heavy defeat in their last match at Hull KR a fortnight ago. Kevin Brown made his debut after his close-season move from Huddersfield and an ankle operation, and he did well before limping off on the hour.
Ben Cross returned from suspension with Phelps, Patrick Ah Van, Frank Winterstein and Ben Kavanagh also back. Out went Shaun Briscoe, Willie Isa, Steve Pickersgill, Dave Allen, Phil Joseph and Macgraff Leuluai.
Hull were still missing key men Gareth Ellis and Daniel Holdsworth but had Brett Seymour returning at scrum-half for his first match since the opening defeat at Leeds. Ben Crooks and Chris Green were also out, with Joe Arundel taking over in the centre and Richard Whiting starting at loose forward.
Hull were seeking their first away win of the season after the Leeds defeat and a draw at St Helens, but it proved far beyond them as they crumbled following a bright opening.
The Black and Whites made a perfect start with Paddy Flynn forced into touch from Joe Arundel's clever kick-off. It took only two minutes for Richard Horne to send Joe Westerman over for a try that the loose forward also converted.
Hull almost extended the lead after Hep Cahill's late challenge on Seymour but Tom Lineham was bundled into touch from Horne's long pass.
Then it needed a try-saving tackle from full-back Rhys Hanbury to deny Tom Briscoe a breakaway touchdown.
Ah Van, making his first appearance of the season for Widnes, proved a handful with his midfield runs but Hull's defence was holding out, with Cross also stopped short.
The Widnes pressure was rewarded midway through the first half with Joe Mellor and Hanbury giving Flynn a chance and the winger cut inside to force his way through three defenders and cut the gap to 6-4.
Gareth Hock spoiled a surging break with a poor pass before Hull went 12-4 ahead after 27 minutes, with Ben Galea taking Seymour's pass to blast through Mellor and Chris Dean.
Widnes cut the gap to 12-10 at the break with a superb solo try from Flynn who intercepted a long Seymour pass to race the length of the field.
Lineham made a gallant attempt to cut off Flynn but the winger had enough speed to reach the line, with Ah Van converting.
Widnes went ahead for the first time almost immediately at the start of the second half, with a thundering Hock break putting Phelps over in the corner. Ah Van's conversion attempt hit the post.
Then Brown's kick was collected by Dean for another Widnes try, with Ah Van's conversion making it 20-12.
Briscoe was stopped by desperate Widnes defence before Brown was forced off.
The loss did not hamper Widnes who extended the lead to 24-12 when Hanbury sent Phelps over for his second try.
Lineham gave Hull some hope after 66 minutes with his first try of the campaign.
But Frank Winterstein went over nine minutes from time to end any doubt, before Hock added the final touchdown as time ran out.