Huddersfield dominated much of the game and forged into a 2-0 half-time lead with fine finishes from Jacob Butterfield and Harry Bunn.
Reading reduced the deficit with an individual effort from Simon Cox with 11 minutes left but Huddersfield clung on for their first win of the season.
Reading were previously unbeaten in three matches, in the league and Capital One Cup, but were again missing eight senior players due to injury or lack of fitness.
A young side – similar to that which beat Ipswich Town 1-0 at home on Saturday – started tentatively and were put under mounting pressure by their opponents.
Huddersfield were without midfielder Oliver Norwood, who is expected to move to Reading by the end of this week, but were the more composed side.
Sean Scannell drove a fierce shot across the face of the home area, with Nakhi Wells only a fraction away from making contact.
Pointless and managerless Huddersfield – Mark Robins having been sacked after the 4-0 home defeat by Bournemouth on the opening day of the season – were looking impressive.
And they deservedly, if somewhat fortuitously, went ahead in the 10th minute, after a sloppy error by Reading centre back Michael Hector.
Hector played a poor pass to Hope Akpan, who was easily dispossessed by Butterfield. The midfielder ran on and curled in a superb shot past home goalkeeper Adam Federici.
Huddersfield went 2-0 up in the 38th minute. Bunn was allowed the freedom of the left flank to cut in and easily place his shot past Federici.
Reading manager Nigel Adkins decided action was needed at half time and brought on 18-year-old midfielder Aaron Kuhl, for his senior debut, in place of left back Shaun Cummings.
But it got little better for the home side. Butterfield drove wide and Federici had to save smartly from Wells and Bunn.
Kuhl began to give Reading a more incisive approach and from his precise cross from the right Cox had a free header, but he nodded it wide.
With Huddersfield content to sit back and take what they had, Reading came more into the game. But their finishing continued to be well off target.
Pavel Pogrebnyak’s close-range attempt took a deflection on its way behind for a corner but Nick Blackman’s effort was badly miscued from 20 yards.
Cox did better soon after, with Huddersfield goalkeeper Alex Smithies having to make a diving save to smother his low shot.
But Smithies could do nothing in the 79th minute when Reading equalised. Cox gathered a loose ball on the edge of the area and let fly with a fine shot.
Alex Pearce lobbed onto the top of the bar with two minutes left but Huddersfield held on.