Imran Tahir ended on 6-108 as Lancashire collapsed on the final day
Lancashire lost their last eight wickets for just 78 runs as Hampshire earned a comfortable win at Liverpool.
Having started the day on 144-2 the home side were undone by leg-spinner Imran Tahir, who took four wickets before lunch and ended with 6-108.
One bright spot was an innings of 54 by England all-rounder Andrew Flintoff, his best since returning from injury.
But it was not enough as Michael Carberry (62) and James Adams (46) wrapped up a 10-wicket victory.
It was the second win of the season for the visitors and lifted them above Lancashire into fourth place in the table.
Flintoff was the first batsman dismissed on the final day when he was caught trying to pull a ball from Dimitri Mascarenhas after 18 to his overnight 36 not out.
It was his first half-century for Lancashire since their Twenty20 Cup quarter-final defeat by Middlesex last July.
VVS Laxman was the next to go, when he was run out for one, having attempted a needless second run to square leg.
Tahir then despatched Kyle Hogg, Steven Croft and Francois du Plessis with Luke Sutton the next to go when he was caught by Chris Benham at third slip off the bowling of Chris Tremlett.
Sajid Mahmood was caught behind off the bowling of Tahir but Glenn Chapple, who ended on 34 not out, demonstrated some resistance by hitting the spinner for two sixes in his first two overs after lunch.
But having been set a target of 117 to win, Hampshire only needed 23.1 overs to complete the job as the hosts chose to restrict Flintoff to a three-over spell with the new ball.
Lancashire all-rounder Andrew Flintoff told BBC Radio Lancashire:
"I was disappointed with the result more than anything. Yesterday, I batted through to last night, got in this morning with a chance to bat for a long time.
"I was a little bit unfortunate with the dismissal but that happens. It's alright getting a 50 but it was disappointing that I only probably did half the job."
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