The Giants fought back from 10-0 down to secure another major scalp and take over at the top of Super League after three rounds with the only 100 per cent record.
Brett Ferres capped a terrific display by Paul Anderson's men with a 90-metre interception try in the last act of a pulsating encounter at the John Smith's Stadium.
Jamie Cording had earlier scored his first Super League try as Huddersfield continued their impressive start to the season, which began with a stunning victory at St Helens.
Wigan's woes began before kick-off when Tomkins pulled out with a shoulder injury yet they initially made light of the absence of their talisman as they split the Huddersfield defence twice in as many minutes to surge into a 10-0 lead.
Second-rower Liam Farrell burrowed his way over for his third try in as many matches before taking Blake Green's defence-splitting pass to romp into space and send makeshift full-back Josh Charnley over. With Pat Richards adding a conversion, Huddersfield had shipped as many points in the first 11 minutes as they conceded in their first two matches.
It took them some time to recover from the shock but, with in-form second-rower Ferres showing the way, the Giants clawed their way back into the game and pulled a try back on 21 minutes when right winger Jermaine McGillvary took Leroy Cudjoe's neatly-timed pass and rounded Richards for a superb try.
Danny Brough's touchline conversion cut the gap to four points and it was all square eight minutes into the second half when substitute Cording exploded onto Shaun Lunt's short pass for his maiden score. Brough's second goal edged the home side in front and he made it 14-10 with a penalty on 55 minutes.
The Giants pushed for the clinching try but they had to settle for a second Brough penalty, this time kicked from 40 metres out. Wigan were not finished, however, and they piled on the pressure in the closing stages in pursuit of a point.
The hosts defended heroically and then, as Richards released a speculative pass 10 metres out from the Huddersfield line, Ferres seized on the ball and held off the cover on a sensational 90-metre sprint to the Wigan line. Brough maintained his accuracy with another touchline conversion, his fifth goal from as many attempts.