Diego Godin's second half header saw Atletico Madrid stun Camp Nou and lift La Liga for the first time since 1996 following its 1-1 draw with Barcelona.
Injuries to Diego Costa (hamstring) and Arda Turan (pelvis) inside the first 25 minutes looked to have damaged Atletico's hopes, and Alexis Sanchez's stunning 34th-minute goal gave Barcelona all the momentum.
But sloppy marking from a corner would ultimately cost the hosts, which allowed Godin to steal in unmarked and head in the all-important equalizer four minutes into the second half.
Lionel Messi had a goal ruled out for offside as the hosts sought a response, but they were ultimately denied by the visitors' typically stubborn defense, as Atleti clinched the title by three points.
The title is Atletico's 10th in the Spanish top flight and ensures it finishes the season unbeaten in all six matches it has played against Barcelona.
And, although Costa and Turan's injuries will reduce its chances of winning next week's Champions League final against bitter rivals Real Madrid, Atletico will first be celebrating the end to its 18-year Liga drought.
Simeone's men led the league by as many as six points in April but stuttered in the run-in, only to produce when it counted in Barcelona, which may have played its last match for under-pressure coach Gerardo Martino.
Passed fit to play despite pre-match doubts, Costa started alongside ex-Barcelona forward David Villa, while the hosts - which surprisingly left out Xavi - recalled Gerard Pique after he recovered from a hip injury sustained against the same opponents last month.
Any suggestions Atletico would play for a draw were quashed in the early stages, as Miranda nodded a free kick wide before Juanfran's dangerous ball into the penalty area had to be cleared by Pique.
But disaster struck for the visitors in the 14th minute as Costa pulled up clutching his hamstring and was forced off.
The striker, who has scored 36 goals in 51 appearances this season, could not control his emotions as he broke down in tears on the bench. He would be joined by Turan nine minutes later when he failed to recover from a pelvic injury sustained in a collision with Cesc Fabregas.
Atletico's double blow gave Barcelona a boost and after a cagey start it started to create chances as Alexis and Pedro failed to convert headers after excellent crosses from Dani Alves on the right.
Pedro's failure to hit the target from a free header was particularly disappointing, but Alexis sent the partisan crowd wild in the 34th minute with his outstanding finish from just inside the area.
Messi chested down a lobbed Fabregas ball and Alexis pounced, thrashing a half-volley past Atletico goalkeeper Thibaut Courtois and into the top-right corner from an incredibly difficult angle.
Tempers frayed before halftime, with four players booked in the 10 minutes before the break, and Atletico came out breathing fire once play resumed.
Villa was the first to go close, firing a left-footed volley into the post after beating Barcelona goalkeeper Jose Pinto with a quick shot on the turn.
The forward was then played in, but under pressure from Alves could not get a shot off before the onrushing Pinto cleared.
Atletico did get its goal four minutes into the second half, as the unmarked Godin made the most of Barca's flat-footed defense to score a towering header from Gabi's corner.
Neymar made his first appearance in more than a month from the bench as Martino chased the game and, in the 63rd minute, Barcelona thought it had taken the lead.
Messi was the man to fire home an instinctive volley - which flew into the roof of the net from close range - only for his effort to be adjudged offside.
Alves had a fierce strike tipped over in the latter stages, but despite late pressure, Atletico clung on and was applauded for its efforts by the Camp Nou faithful at full time amid wild celebrations from the small contingent of away supporters.
Start your workday the right way with the news that matters most. Learn more