Eric Dier's 39th-minute header set Spurs on course for a win that would have seen them supplant Manchester United in fourth place in the table, only for Mitrovic to poke home a 74th-minute equaliser just two minutes after coming on.
Worse was to follow for the hosts as Perez struck a stoppage-time winner that saw Newcastle register a third successive league win at White Hart Lane -- something they last achieved in 1911 -- and, more importantly, lifted Steve McClaren's men out of the relegation zone.
Spurs were seeking to go 15 successive top-flight games without defeat for the first time since 1967, but instead succumbed to their first loss since a 1-0 reverse at United on the opening day, leaving Mauricio Pochettino's side three points below the Champions League places.
Harry Kane was one of several first-team players recalled by Pochettino following Thursday's 4-1 Europa League win over Monaco and he showed his intent with a low first-minute shot that forced Newcastle goalkeeper Rob Elliot to save one-handed.
At the other end, Papiss Cisse inadvertently blocked a goal-bound effort from team-mate Siem de Jong with his face, but Spurs were soon back on the front foot, Dier dragging a shot wide from outside the box.
Elliot denied Erik Lamela twice in the space of two minutes, first springing to his left to paw away a shot from the edge of the box and then tipping a prodded effort over the bar following a flick-on by Kane.
But from the corner that followed the second chance Spurs took the lead as Dier stole in front of his marker at the near post to glance Christian Eriksen's left-wing corner past Elliot.
Danny Rose could have extended Spurs' lead before the interval, but when Eriksen's shot deflected into his path via Fabricio Coloccini's backside, his shot bisected the goal and the sliding Kane.
Newcastle manager McClaren resisted the urge to make any changes at half-time and saw Cisse go close early in the second period when he drilled narrowly wide with his left foot from Moussa Sissoko's pass.
Spurs continued to probe at the other end, however, with Elliot fully extended by a 25-yard effort from Kane and also obliged to field a couple of long-range attempts from Eriksen.
McClaren sent on Mitrovic for Cisse with 18 minutes left and the combative Serbian striker made an immediate impact, poking home from right on the line after Chancel Mbemba's stooping header was parried by Hugo Lloris.
Mitrovic squandered a chance to put Newcastle ahead when he failed to apply a touch to Sissoko's inviting cross in the final minute.
But fellow entrant Perez spared his blushes three minutes later, squeezing a shot beneath Lloris at his near post to earn Newcastle back-to-back league wins for the first time since November last year. – AFP
Original source: Newcastle subs sink Spurs