More chances followed in extra time, but it was Mario Mandzukic who made himself the hero with a 109th-minute winner to send Croatia into the final of the World Cup for the first time ever, where they will face France on Sunday.
England, meanwhile, are condemned to a third-place playoff against Belgium on Saturday having fallen to a fourth consecutive semi-final defeat.
Gareth Southgate named the same starting XI for the third match in a row, and it took just five minutes for England to take the lead in front of a vastly-increased crowd to the one which saw them beat Sweden in the quarter-finals.
Luka Modric's foul on Dele Alli gifted the Three Lions a free kick in a dangerous position early on, and Trippier stepped up to bend the ball over the wall and into the top corner, leaving Croatian goalkeeper Danijel Subasic rooted to the spot.
In doing so, Trippier joined an exclusive club including only Sir Bobby Charlton and Gary Lineker as the only Englishmen to score in a World Cup semi-final, while his goal also saw England break their national record for most goals at a single World Cup.
More importantly, though, it gave England a dream start to their first semi-final in 28 years, and they kept the early pressure on as Croatia were slow to get going.
Harry Maguire's threat at set pieces was as constant as ever and the Leicester City centre-back had one sighter before planting a downward header narrowly wide of the target after 14 minutes.
A couple of Perisic pot-shots from range was all an out-of-sorts Croatia could muster in the opening 30 minutes, and England should have doubled their advantage on the half-hour mark when World Cup top-scorer Harry Kane was slipped through on goal, only to be denied by Subasic when one on one and then a combination of both Subasic and the post from point-blank range.
It took 32 minutes for Jordan Pickford to be called into action for the first time, and even then it was a straightforward stop from the England keeper to deny Ante Rebic's curling effort after Maguire had failed to clear his lines.
It was England that created by far the best chances of the first half, though, and another went begging with nine minutes remaining until half time when Kane and Alli combined to tee up Jesse Lingard, who curled the ball wide of the target when he should have done better.
Southgate's side went into half time knowing that they could have - and should have - been further in front, but they continued to look the most likely at the start of the second half too and Lingard saw one deflected strike loop over the crossbar before only a fine last-ditch challenge from Dejan Lovren prevented Kane from converting another sublime Trippier delivery.
England struggled to maintain their first-half momentum, though, and Croatia's threat slowly began to grow, with Kyle Walker needing to make a brave block to deny Perisic from the edge of the box.
Croatia's breakthrough finally came with just over 20 minutes remaining of normal time when Perisic got in front of Walker and steered the ball past Pickford with an inventive finish after Sime Vrsaljko had been given time to swing his cross into the box.
The equaliser breathed new life into Croatia and they should have taken the lead just four minutes later when a defensive error gifted the ball to Perisic, who beat Walker before drilling a low strike against the far post. The ball rebounded straight out to Rebic, but he could only fire the rebound into the grateful arms of Pickford.
Moments later England were caught sleeping from a short corner to which Maguire reacted in time to clear as far as Marcelo Brozovic, whose first-time effort from range flew over the crossbar to hand Southgate's side a brief respite.
Lingard and Jordan Henderson both missed the target with sights of goal as England looked to stem the tide, but it was Croatia that ended normal time on top and Mandzukic stung the palms of Pickford with a volley after taking down Brozovic's clever ball on his chest.
Moments later Pickford failed to clear his lines with a punch and gifted the ball straight to the ever-dangerous Perisic, who could not adjust his body in time to steer his effort into the empty net.
England were hanging on in the closing stages, although they did have a half-chance to steal victory inside the 90 minutes when Kane got on the end of Trippier's stoppage-time free kick, only to send his header comfortably wide as the match went into extra time.
The Three Lions managed to steady themselves again for the first period of extra time, after being on the ropes for much of the second half, and they were inches away from regaining their lead when Vrsaljko was in the right place to clear a header from an unmarked John Stones off the line.
It took a similar piece of heroism from Pickford at the other end to keep the scores level in stoppage time of the first half of extra time when Perisic's wicked delivery appeared to lay the ball on a plate for Mandzukic, only for the England keeper to fly out and make a sensational save from point-blank range.
Croatia's pressure continued into the second period of extra time, though, and Brozovic spurned one good chance moments before England were finally punished for their tired defending.
A Perisic header caught Stones flat-footed as the ball bounced through to Mandzukic, who was sharp enough to latch on to it and sweep his finish beyond Pickford.
Despite going to penalties in both of their previous World Cup knockout games this year Croatia continued to look the fresher of the two teams, and they could have added further to their lead through efforts from Brozovic and Kramaric.
England struggled to muster anything in response as their memorable World Cup run came to end with them missing the chance to reach the final for the first time since 1966.
The Three Lions will now face Belgium in the third-place playoff on Saturday, before Croatia take on France in the World Cup final on Sunday afternoon.
CROATIA (4-5-1): Subasic; Vrsaljko, Lovren, Vida, Strinic (Pivaric 95'); Rebic (Kramaric 101'), Modric (Badelj 119'), Brozovic, Rakitic, Perisic; Mandzukic (Corluka 115')
ENGLAND (3-1-4-2): Pickford; Walker (Vardy 112'), Stones, Maguire; Henderson (Dier 97'); Trippier, Lingard, Alli, Young (Rose 90'); Kane, Sterling (Rashford 74')