The Giants re-discovered the form that enabled them to top the table after 12 rounds as they completed their first league double over Leeds for more than half a century.
Huddersfield's biggest-ever Super League win over the Rhinos was a personal triumph for newly-appointed captain Danny Brough, who created his side's first two tries, scored a solo effort and kicked eight goals from 10 attempts for a 20-point haul.
And it came despite playing for 65 minutes a man short after the dismissal of forward Luke O'Donnell for a challenge on Leeds prop Ian Kirke which caused a 10-minute stoppage in play.
Kirke, a member of Leeds' Challenge Cup final team, had been introduced from the bench only moments earlier but he was forced to undergo lengthy treatment on the field before being despatched to hospital.
O'Donnell, who was also sent off against Leeds last season, received his red card from referee Thierry Alibert in farcical circumstances.
After initially allowing play to continue, Alibert stopped play after the next tackle to enable Kirke to receive treatment and, during a 10-minute stoppage, he delivered a warning to O'Donnell.
The Australian forward was then replaced by substitute Larne Patrick but several minutes later was recalled to the field by Alibert and, once Kirke had been carried from the field on a stretcher, was shown the red card.
Huddersfield were leading 10-0 at that stage after making a blistering start to their final game of the regular season with two tries in the first seven minutes.
Brough put full-back Leroy Cudjoe through a gap for the opening score and then hoisted a towering kick for left winger Luke George to claim his 15th try of the campaign.
Even down to 12 men, the Giants were much the livelier team and they stretched their lead after 28 minutes when right winger Jermaine McGillvary palmed back Brough's kick to the corner for centre Michael Lawrence to touch down.
Brough's second conversion brought up his 1,000th point but there was little sign of the points feast to come.
Leeds hinted at a fightback when skipper Kevin Sinfield combined with Weller Hauraki to get centre Jimmy Keinhorst over for a try, but Brough crucially struck on the stroke of half-time, intercepting Carl Ablett's pass to scoot 30 metres for an opportunist score.
Brough's conversion made it 22-4 and he increased his side's lead with two penalties early in the second half before second rower Brett Ferres broke clear to get hooker Luke Robinson over.
The Rhinos pulled a try back on the hour through winger Ryan Hall but Huddersfield simply went up a gear to produce some breathtaking rugby.
Stand-off Scott Grix touched down Brough's grubber kick and then flipped up a 'miracle' pass for Robinson to claim his second try.
Cudjoe then finished off a glorious passing move to register his side's eighth try which made it 48-10.
The Rhinos staged a late rally which brought further tries to centre Kallum Watkins, Ablett and prop Jamie Peacock but they were little more than consolation efforts for the well-beaten champions.
Widnes ended up with the wooden spoon in their first season back in Super League after a thumping derby defeat to Warrington.
The Vikings needed a shock win over the Challenge Cup winners to climb above Castleford but were outplayed after being level 6-6 midway through the first half.
Warrington scored 10 tries and the winning margin would have been even more convincing had they not missed four first-half conversion attempts.
Chris Riley and Mickey Higham each grabbed a brace of touchdowns for the Wolves who host St Helens on Saturday in the play-offs.
Widnes, who had conceded 114 points in two previous defeats by Warrington this season, went into the clash without Hep Cahill following shoulder surgery.
Shaun Briscoe and Danny Craven were left out with Jack Owens, Macgraff Leuluai, Chris Dean and Joe Mellor returning.
Warrington, fresh from a 54-6 romp over Huddersfield, rested skipper Brett Hodgson, Garreth Carvell, Trent Waterhouse and brothers Michael and Joel Monaghan with Ben Westwood still out with after a knee injury sustained in the cup final win over Leeds a fortnight ago.
Chris Riley, David Solomona and Tyrone McCarthy were back as Warrington aimed for their seventh win in the last eight Super League matches.
Widnes had won only one of their last five games - against Hull three weeks ago - but made a flying start with Frank Winterstein going over in the corner after four minutes from Jon Clarke's short pass on the blind-side.
Rhys Hanbury booted the touchline conversion but Warrington were back on level terms after 10 minutes when Higham burrowed over from dummy half and Lee Briers tagged on the goal.
The Vikings, who had lost all five derby meetings since 2004, were certainly not overawed although Paddy Flynn was forced to pull off try-saving tackles on Stefan Ratchford and Riley in quick succession.
But Briers' long pass to Simon Grix allowed Chris Bridge to hand Rhys Williams a walk-in try midway through the first half to open up a 10-6 advantage.
Widnes faced a bigger task after inspirational play from Ratchford who burst onto a pass and then kicked ahead for Riley to touchdown after 28 minutes for the 100th try of his career.
Ratchford was in top form and extended the lead when he raced onto an inside pass from Solomona to cross. Briers, after two misses from three goal attempts, handed over the duties to Ratchford who was narrowly off-target aiming to convert his own try.
Solomona added Warrington's fifth try just before the break to make it 22-6 at half-time with Riley supporting Matty Blythe's break straight after the restart to bag his second try with Briers booting the goal.
Blythe was a half-time replacement for the impressive Ratchford who had linked up superbly from full-back.
Paul McShane notched the Vikings' second try but was injured in the process and forced to hobble off with a leg injury.
Higham collected his second touchdown from a Williams kick after 66 minutes to make it 40-10.
Widnes refused to throw in the towel with Ben Davies held close before Rhys Hanbury went over for a deserved effort in front of a 8,617 crowd - the Vikings' biggest of the season.
Warrington wrapped up the convincing win with late tries from Ryan Atkins and Paul Wood - his first of the season - with Solomona booting the final conversion.