Paul Cullen?s Wolves stormed 16-0 ahead with three tries in the opening 15 minutes to delight the majority at a packed Halliwell Jones Stadium.
But thereafter Saints assumed complete control by running in five tries during a blistering spell to lead 28-16 at the break and leave Warrington stunned.
It was an astonishing turnaround which gave the Powergen Challenge Cup holders an advantage they did not surrender and further encouraged hopes that a Grand Slam is eminently possible.
Saints simply do not lose against Warrington and this was their 24th win from 27 Super League encounters from their rivals across the M62.
Warrington?s last victory against the Knowsley Road club came in April 2001 and this latest defeat ensured they will now face a tough trip to Leeds Rhinos on Friday in the play-offs.
Victory would have handed Wolves fifth spot and a visit to Bradford Bulls ? a ground they have already won on this season ? but instead a showdown at Headingley Carnegie awaits.
Warrington, so maddeningly inconsistent, were hammered 54-16 at Leeds at the beginning of the month and will not relish a trip to the home of the Rhinos.
However, they can at least take encouragement from their attacking finesse during the opening 15 minutes when they threatened to finally smash the Indian sign which Saints have held over them for so long.
Not surprisingly, skipper Lee Briers provided the Wolves? inspiration during their early dominance and his neat offload sent prop Paul Wood bustling over the line after just three minutes.
Warrington extended their lead lead four minutes later when a bewildering array of inter-passing saw the ball pass through Briers, Chris Bridge, Ben Westwood and Toa Kohe-Love and culminated in Richie Barnett crossing in the left corner.
The Wolves were dominant and their third try in the 17th minute was indicative of their control.
Briers, who converted three of his side?s six tries, again played his part with a teasing grubber kick which the impressive Westwood touched down.
St Helens had barely escaped their own half at this point but they gained some much-needed respite with a try after 18 minutes through Jon Wilkin, who shrugged aside stand-in full-back Henry Fa?afili to race over the line.
Saints began to move through the gears and some typically spellbinding handling saw the ball go through five players and led to Ade Gardner touching down in the 27th minute.
Three minutes later, a fine attacking move out wide on the left saw Leon Pryce and Francis Meli combine to send the supporting Paul Wellens over.
Warrington simply could not cope with Saints? potency and further scores from Wilkin and Wellens sent the visitors in at the break with a 28-16 advantage.
To their credit, Warrington continued to battle and tries from Kohe-Love and Martin Gleeson dragged them right back into contention at 24-28 with half an hour remaining.
However, Saints simply responded in the only way they know how with two more clinical scores from Willie Talau and Vinnie Anderson.
Those tries gave the visitors a little breathing space at 38-24 but Bridge?s 72nd-minute score took Warrington to 30 points and prompted a late rally.
But St Helens, for whom potent centre Lyon converted five of seven scores, held firm.
Warrington: 30 (16). Tries: Wood, Barnett, Westwood, Kohe-Love, M. Gleeson, Bridge. Goals: Briers 3.
St Helens: 38 (28). Tries: Wilkin, Gardner 2, Wellens 2, Talau, V. Anderson. Goals: Lyon 5.
Warrington: Riley, Fa?afili, M. Gleeson, Kohe-Love, Barnett, Bridge, Briers, Wood, Sullivan, Rauhihi, Swann, Wainwright, Westwood. Replacements: Penny, M. Gleeson, Parker, Cooper.
St Helens: Wellens, Gardner, Lyon, Talau, Meli, Pryce, Long, Cayless, Cunningham, P. Anderson, Gilmour, Wilkin, Bennett. Replacements: Roby, V. Anderson, Graham, Fa?asavalu.
Referee: A Klein (London)