Yousuf erased West Indian Vivian Richards' 30-year landmark and set a new record of 1,788 Test runs in 11 Tests during 2006 with his masterly 124, his ninth century of the year.
Pakistan declared their second innings at 399-6 with captain Inzamam-ul-Haq unbeaten on 58, giving the tourists a mammoth 444-run target at the National Stadium on Thursday.
The West Indies finished the fourth day at 39-2, needing another 405 runs to win or bat the whole fifth day to draw the match. Captain Brian Lara was unbeaten on 18 and Ramnaresh Sarwan was 11 not out.
Pakistani opener Mohammad Hafeez's watchful and valuable innings of 104 was overshadowed by Yousuf's record-breaking feats as the pair added 149 runs for the third wicket.
On 44 Yousuf drove West Indian paceman Corey Collymore to long-on for his ninth boundary to cross Richards' record tally made in 1976. The 32-year-old achieved the new mark in 11 Tests, the same number it took the West Indian great.
Yousuf raised his bat and looked to the sky as Lara, who had pledged his side would try to protect his legendary predecessor's record, applauded the Pakistani and went to congratulate him at the end of the over.
The West Indies were again sloppy in the field as Ganga grassed Yousuf in the penultimate over before lunch off part-timer Ramnaresh Sarwan, when the batsman was on 68.
Paceman Jerome Taylor then spilled a simple chance off his own bowling when Yousuf was on 87. Yousuf once again capitalised on the fumble to punish the West Indian bowlers.
Yousuf hit paceman Dwayne Bravo for his 14th boundary to reach his 23rd Test century off just 125 balls -- his second of the match.
It meant he beat his own record of eight Test centuries in a year, set with his fighting 102 in the first innings. The previous mark of seven was held by Richards (1976) and Sri Lanka's Aravinda de Silva (1997).
Yousuf was finally bowled round his legs by part-timer Ramnaresh Sarwan. He hit 15 boundaries during his 294-minute knock.
Meanwhile Hafeez, also dropped by Bravo on 103, reached his second Test century with his 10th boundary off Taylor, before the fast bowler forced an edge for Denesh Ramdin to take a catch behind the stumps.
Pakistan lost Shoaib Malik and Abdul Razzaq for 10 each before Inzamam, who scored his only 50 of the series, declared the innings.
Yousuf became the sixth Pakistani batsman to score a century in each innings of a Test, following Hanif Mohammad, Javed Miandad, Wajahatullah Wasti, Inzamam and Yasir Hameed.
When on 43, Yousuf further surpassed the Pakistan record for the most runs in a three-match series, set by former great Zaheer Abbas with 583 made against India in 1978. Yousuf's series total is 665.
And he equalled Australian great Don Bradman's record of scoring six centuries in successive Tests -- although it took Yousuf only five matches compared with Bradman's six.
Yousuf has now scored four hundreds in five innings against the West Indies since his 192 in Pakistan's nine-wicket win in the first Test in Lahore. He also made 191 in the drawn second Test at Multan.
Pakistan 304 and 399 for 6 decl (Mohammad Yousuf 124, Mohd Hafeez 104, Inzamam-ul-Haq 58 n o; Sarwan 2 for 70, Gayle 1 for 38) Vs West Indies 260 and 39 for 2 ( Lara 19 n o, Sarwan 11 n o; Nazir 1 for 9, Gul 1 for 25)