Only a Don Bradman-inspired Australia, who made 404 for three back in 1948, have ever scored more in the fourth innings to win a Headingley Test.
Read, recalled for this match after a two-year Test exile, came to the crease when England - 1-0 up in the four-match series were 248 for five, a still far from insurmountable lead of 225 which owed much to 116 from captain Andrew Strauss.
But a stand of 51 with Paul Collingwood strengthened England's position before Read himself was last man out having played on to Mohammad Sami, the hosts dismissed for 345.
At Monday's stumps Pakistan were nought without loss, Salman Butt and Taufeeq Umar the undefeated batsmen, setting up a fascinating final day.
England skipper Strauss said the home side would attack the tourists early as they sought to seal the series.
"The guys are going to go out all guns blazing," Strauss said. "It's got the potential to be a really good day. We're hopeful of getting a result.
"The wicket misbehaved a bit when the new ball was used today and hopefully it will misbehave tomorrow.
"We have to take it one over at a time. We don't need to get carried away -- the key thing will be patience."
England were the only other team to score more than 300 for victory in the final innings of a Headingley Test, making 315 for four against Australia five years ago.
They resumed after tea on 237 for four, a lead of 214, after Strauss had fallen for 116 to the last ball before the break.
England lost their fifth wicket when Ian Bell (four), who'd made 119 in his side's first innings 515, got an inside-edge to a Sami delivery and wicket-keeper Kamran Akmal, who'd dropped two easy chances offered by Marcus Trescothick, held a fine diving catch to claim his 100th Test victim.
Read in for the dropped Geraint Jones because of his rival keeper's lack of runs, had scored 150 not out for England A against Pakistan this season.
Long regarded as a better gloveman than Jones, Read showed his improved batting form by lofting leg-spinner Danish Kaneria for six.
Read did have a reprieve of sorts when, on 45, he was caught at mid-on off an Umar Gul no-ball.
He then completed his half-century in 78 balls when he pulled pace bowler Gul for his sixth four.
England had lost two quick wickets to be 301 for seven.
Collingwood played on to Shahid Nazir and the medium-pacer, playing his first Test in seven years, then had Sajid Mahmood (two) caught behind on his way to impressive figures of three for 32 in 14 overs.
Strauss's hundred was his 10th in just 30 Tests but he was still left searching for his first score in excess of 150 at this level after he was caught behind trying to leave a Sami delivery.
England had been strongly placed at 158 without loss before five wickets fell for 90 runs.
Strauss's fellow left-handed opener Trescothick went for 58, before Alastair Cook (21), taken at short leg, and Kevin Pietersen (16), bowled through the gate by a googly, both fell to Kaneria.
Trescothick and Strauss resumed after lunch both on 54 not out.
Trescothick's luck then ran out when he got the toe end of his bat to a wide Gul ball and Butt, at second slip, took a sharp catch.
Strauss, who made 128 in the drawn series opener at Lord's, then went to his century in 153 balls with his 13th four, with a trademark cut down to third man off Sami.
In the morning Trescothick had been missed on six and seven by Akmal - when England were still behind.
Three overs into the day's play he flicked at Sami but Akmal reacted slowly to the gloved legside chance and only got one hand to the ball.
Next over Akmal spilled an even easier catch when Gul produced a superb lifting delivery which took the outside edge of Trescothick's bat only for Akmal to drop the routine chance despite getting both hands to the ball.
Pakistan, who made 538, were 23 runs ahead on first innings after a third-wicket stand of 363 between Younis Khan (173) and Mohammad Yousuf (192), their country's best Test partnership against England.
Pakistan captain Inzamam-ul-Haq's lengthy absence with a chest injury Monday meant he was unlikely to be allowed to bat higher than number seven in his side's second innings.