The tourists finished on 1-96 after losing stand-in skipper Ollie Pope for a second ball duck in the second over. Pope was only opening as Ben Duckett suffered a thumb injury catching Pakistan's last wicket.
Zak Crawley led England's reply with a run-a-ball 64 not out while Joe Root is on 32 at the other end.
England's Zak Crawley and Joe Root walk off at Multan after posting 1-96 in reply to Pakistan's 556. (AP PHOTO)
Earlier Salman Ali Agha became the third Pakistan batter to smash a hundred in the match before being left not out on 104 as Pakistan were all out in the final session.
Pakistan had started the day on 4-328 with Naseem Shah at the crease as a nightwatchman. Underlining the ease of batting he smacked three sixes in his career-best 33, denying England a breakthrough in the first hour, despite suffering hits to the helmet and his bowling hand.
Naseem collaborated in a 64-run partnership with Saud Shakeel before he tickled Brydon Carse to Harry Brook at leg slip, giving the debutant seamer his maiden Test wicket.
Mohammad Rizwan then fell for a 12-ball duck, stepping out against Jack Leach and spooning the ball to Chris Woakes at mid-off.
But that only brought in Salman who upped the scoring rate before and after Saud departed for 82, caught in the slip off Shoaib Bashir.
Thanks to Salman's free-scoring knock, Pakistan milked 118 runs from 26 overs in the afternoon session.
Salman Ali Agha peforms Sajdah, a prayer bow in gratitude to God, after scoring his century. (AP PHOTO)
Salman, who hit it 10 boundaries and three sixes in his 119-ball knock, kissed the turf after reaching his third Test hundred. He had survived a brilliant one-man relay catch by Woakes, who the third umpire judged just had a toe on the ground outside the boundary as he leapt back inside to grab the ball.
"I believe I can take on spinners, no matter what the situation is, and that's exactly what I did," Salman said.
"I have been playing with tailenders for the last two years, so when the tail comes it brings the best out of me."
After 104 unsuccessful bouncers England finally took a wicket with one to wrap up the innings - a surprise bumper from off-spinner Root. Abrar Ahmed edged it to Duckett but the opener injured his thumb in the process.
Infuriatingly for England Duckett should never have been exposed, Abrar had survived a botched stumping by Jamie Smith and dropped catch from Gus Atkinson in the previous few minutes.
The errors betrayed their growing fatigue in draining conditions.
"Last two days have been immensely tough conditions for everyone out there," Carse said.
"We didn't get that much out of it (pitch) over the couple of days, but credit to the team and everyone for keep coming back. There's some tired bodies, but the lads will rest up and come again tomorrow."
England expect Duckett to bat at some point but Pope, deputising, was soon out. He pulled Naseem and Aamer Jamaal plucked a one-handed blinder at mid-wicket.
Thereafter England scored at five-an-over but still need another 261 to avoid the follow-on.
with PA
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