In a dominant display, Reading took the lead in the fourth minute when striker Sam Baldock forced the ball home following a corner.
Hull rarely threatened and were breached again midway through the second half, when top scorer Jon Dadi Bodvarsson slotted in from close range.
Defender Andy Yiadom added Reading's third goal in the 81st minute, though the hosts did lose centre back John O'Shea to a red card two minutes later.
Reading had lost 2-1 to Norwich at Madejski Stadium on Wednesday.
It was the first time in the club's 147-year history that they had lost their opening four home league games of the season.
Hull lost 2-1 at Wigan on Tuesday, a fifth defeat in eight Championship outings this term.
Head coach Nigel Adkins returned to Reading for the first time since he was sacked as manager in December 2014.
It was Reading who looked the brighter in the early exchanges, with Bodvarsson scuffed a shot wide and Hull defender Eric Lichaj doing well to clear a dangerous cross from Leandro Bacuna.
But Reading were soon ahead, going in front in only the fourth minute following a Bacuna corner.
Saeid Ezatolahi's clever near-post header draw a fine save from Hull goalkeeper David Marshall but Baldock was on hand to jab in his third goal of the season from close range.
Hull had shown little going forward but gradually worked their way into the game, with Jarrod Bowen sending an angled drive narrowly wide.
However, Reading quickly regained the initiative and Marshall did well to tip over a fierce 25-yard free kick from Bacuna.
Hull striker Fraizer Campbell then cleared off the line from a goal-bound Bodvarsson header after a Bacuna corner.
Reading began the second half in much the same vein as they ended the first, putting pressure on the Hull defence.
But it was the visitors who created the first opening after the interval, when Todd Kane ran through only to be denied by a last-ditch tackle by Tiago Ilori.
Reading gradually regained their control and were rewarded in the 70th minute when they doubled their lead.
Good work by Mo Barrow and Yiadom on the left allowed Bodvarsson the space to guide his shot past Marshall for his fifth goal of the season.
Yiadom then settled it with nine minutes left, swivelling in the Hull area to slot in his first goal for the club.
O'Shea was sent off two minutes later, for a last-man foul on former Reading loanee Chris Martin, but the hosts eased to a second win of the campaign.