Pakistan's Mohammad Rizwan (right) plays a shot as England's wicketkeeper Phil Salt watches in Karachi. AFP
Haris Rauf grabbed three wickets as the hosts tied the seven-match series.
Earlier in-form opener Mohammad Rizwan struck a brilliant 88 as Pakistan made 166-4.
With England needing five for victory from 10 balls, Rauf dismissed Liam Dawson (34) and Olly Stone off successive deliveries in the 19th over.
Last man Reece Topley was then run out as Pakistan rescued victory from almost certain defeat at a packed National stadium in Karachi.
England’s Olly Stone is clean bowled by Pakistan’s Haris Rauf (not pictured) at the National Cricket Stadium. AFP
Dawson had silenced a 32,000 holiday crowd by cracking four fours and a six off pacer Mohammad Hasnain’s 18th over.
When Topley was run out off the second ball of the last over it sent Pakistan players and home fans into raptures.
The win made the occasion of Pakistan’s 200th T20I more memorable. They are the first team to reach the milestone.
England were rocked by Hasnain (2-40) and Nawaz (3-35) and were staring at defeat at 130-7 before Dawson added 32 with Adil Rashid (three not out) to bring England back in the game.
But Rauf’s two wickets, he finished 3-32, sealed the match for Pakistan.
The remaining matches are in Lahore (September 28, 30 and October 2).
England, who are on their first tour of Pakistan for 17 years, won the first and third games while the home team won the second and fourth -- all in Karachi
Rizwan was once again the anchor for Pakistan.
Pakistan’s players celebrate their victory at the National Cricket Stadium in Karachi on Sunday. AFP
He put on 97 for the opening wicket with his captain Babar Azam (36) but England pulled back the scoring rate once the Pakistan skipper holed out to spinner Liam Dawson in the 12th over.
Azam hit three fours off 28 balls.
Rizwan then added 52 for the second with Shan Masood (21) but David Willey dismissed Masood. Topley then had Khushdil Shah for two.
Rizwan was finally caught off in the 19th over off Topley who finished with 2-37.
Asif Ali smashed two sixes in the final over of the innings, runs that proved crucial.
England started badly as Nawaz dismissed opener Phil Salt off the fourth ball of the innings for eight. Then Hasnain accounted for Alex Hales for five and Will Jacks for nought in the second to leave England reeling at 14-3.
Harry Brook, who top-scored with 34, added 43 with Ben Duckett (33) for the fourth wicket and another 49 with skipper Moeen Ali (29) but Nawaz removed both his partners to give Pakistan a sniff of victory.
Brook hit a six and two boundaries off 29 balls. Meanwhile, England’s express pace bowler Mark Wood has declared he is keen on playing Test cricket following his match-winning performance against Pakistan in the third T20I at the National Stadium.
Wood, who is returning to the England white-ball side following two elbow surgeries and an agonising wait of six months, had superb figures of 4-0-24-3 as the Moeen Ali-led side demolished Pakistan to win by 63 runs after Ben Duckett and Harry Brook had scored unbeaten half-centuries.
Wood’s 97-mile-per-hour delivery caught the attention of the fans worldwide, with experts saying he could come in handy in Tests as well under the new setup of coach Brendon McCullum and skipper Ben Stokes. The 32-year-old has taken 82 wickets in 26 Tests and, ironically, his overseas record -- 41 wickets at under 25 runs apiece -- is better than at home.
Pakistan’s Mohammad Rizwan celebrates after scoring a half-century against England during their fourth T20 match at the National Cricket Stadium in Karachi on Sunday.
Pakistan gained favour with the ECB in going ahead with their tour of England earlier this year — as did the West Indies.
Babar Azam led from the front as Pakistan beat England by 31 runs in the first Twenty20 international at Trent Bridge on Friday despite a blistering hundred from Liam Livingstone.
Brook scored a 35-ball 81 not out while Duckett cracked an unbeaten 42-ball 69 to lead England to an impressive 221-3 in their 20 overs after they were sent in to bat at National stadium.
"The PCB and ECB are in discussions regarding the commencement of the 1st #PAKvENG Test as some England players are down with viral infection," the board said on Twitter. "The PCB continues to monitor the situation, is in contact with the ECB.."
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