Pakistan removed the obdurate Darren Bravo late on the third day of the first day-night Test to reinvigorate their cause after a dogged West Indies batting display in Dubai on Saturday.
Bravo defied a potent bowling attack to score 87 during a 402-minute stay at the crease while Samuels made 76 as the West Indies closed on 315-6, still trailing Pakistan's first innings total of 579-3 declared by 264 runs.
Shane Dowrich was unbeaten on 27 with skipper Jason Holder 10 not out at the close of play.
West Indies need to reach 380 to avoid following-on, but the duration of their innings suggests Pakistan captain Misbah-ul-haq may not enforce it and bat again on Sunday.
Bravo and Samuels were engaged in a resolute 113-run stand for the third wicket as the Dubai stadium pitch did not offer much help to Pakistan's attack.
When it looked Bravo would remain unbeaten and complete his eighth hundred he fell to a lazy push off left-arm spinner Mohammad Nawaz and was caught by Azhar Ali at forward short-leg for the debutant's first wicket.
Bravo hit nine fours and a six during his 258-ball vigil.
Bravo had added another 77 for the fourth wicket with Jermaine Blackwood (37) but fiery paceman Wahab Riaz took two quick-fire wickets after Pakistan took the second new ball with the score at 229-3.
Leg-spinner Yasir Shah and Riaz finished with two wickets apiece, with the latter explaining that dew made it tough for the bowlers.
"The ball got wet because of the dew yesterday and when we came today it had gone soft so it was wet, so there was no help for the bowlers and that's why it was tough to get wickets, but we will do our best to effect a result," said Riaz.
Samuels hit two boundaries off the first two balls he faced, driving powerfully off Shah and settling down quickly on a flat pitch.
He took a single off Nawaz to reach his 24th Test fifty and continued in an aggressive style with 13 boundaries.
Samuels looked set for his first hundred since April last year but fell leg-before to paceman Sohail Khan when he missed an inswinging delivery and was caught plumb in front.
Samuels praised his team's resolute approach after spending the best part of two days in the field.
"We played Test cricket today," said Samuels. "We were patient, put away the bad balls, picking singles here and there and this is the way it should be played so we must continue that."
Pakistan had looked for early breakthroughs after the West Indies started the day at 69-1 and were rewarded when Shah bowled Kraigg Brathwaite for 32 with a delivery which turned slightly and beat the bat.
Pakistan's big total was built around opener Azhar Ali's unbeaten 302, his country's fourth triple century.
The remaining two Tests will be played in Abu Dhabi (October 21-25) and Sharjah (October 30-November 3).