After 135 years of predominantly lower league football, coming close to the top-flight a handful of times in the 20th century, the Royals roared into the Premier League in record-breaking fashion with 106 points in 2005/06.
Only three players were added in the summer of 2006 ahead of the opener, Seol Ki-Hyeon the only one to start against Gareth Southgate's Boro as Steve Coppell opted for consistency from that of the title-winning campaign.
Almost 24,000 were crammed into the stadium for the momentous occasion on August 19 2006, Boro no easy start after reaching the final of the UEFA Cup in May 2006.
It looked an ominous start against the Teessiders as they raced into a two-goal lead. England international Stuart Downing scored the first top-flight goal in RG2, volleyed a deep cross to the back post past Marcus Hahnemann.
It went from bad to worse 10 minutes later as future Royal Yakubu was on hand to turn past Hanhemann from close range after a free-kick was too hot to handle.
Looking like deer caught in headlights, it was a far-cry from the confident side that breezed through the Championship.
The tide turned when Nicky Shorey enjoyed a driving run through the Middlesbrough half before setting Kevin Doyle through, his shot forcing Mark Schwarzer into a strong save and proving to the home players and supporters that they could bloody a few noses in the Premiership.
Shorey came close again from a trademark free-kick before Dave Kitson scored a goal 135 years in the making, turning in from Ki-Hyeon's cross to half the deficit and score the Royals' first top-flight goal.
Within another minute, Sidwell got in on the act himself and swept an Ivar Ingimarsson cross past the Australian keeper to miraculously see the two sides head into half-time level.
The turnaround was complete just 10 minutes into the second half, Leroy Lita slamming into an unguarded net after a scramble in the box.
Voted the best match in the history of the SCL Stadium, it set the tone for what would be the greatest season in the club's 154-year existence, finishing eighth in the Premier League and just missing out on a place in Europe on the final day.
The likes of Chelsea, Manchester United, Tottenham Hotspur, Manchester City, Chelsea and Liverpool would fail to beat Coppell's side on home turf over the coming two years, but Middlesbrough will forever be the first victims of Reading as a top-flight outfit.
Reading may well return there one day, a day which feels a long way away at the time of writing as Noel Hunt's side prop up the third tier, but this will forever be in the record books as the first.