Floundering at 55 for two after losing two quick wickets just before tea, West Indies were revived by Brathwaite’s top score of 65 and Samuels’s 60, to reach 147 for two when bad light ended play at 5:45 pm at St George’s Park.
The pair have so far added 92 for the third wicket, a partnership that proved critical after opener Devon Smith (22) and Leon Johnson fell in successive deliveries to seamer Morne Morkel, in the third over before the tea interval.
However, Brathwaite remained steady, carving out his seventh Test half-century in his 16th match, facing 125 balls and striking eight boundaries.
Samuels, meanwhile, took the attack to the South African bowlers, hitting nine fours in an innings that has required just 92 deliveries.
Their combined efforts left West Indies 270 runs behind on first innings, after South Africa declared on 417 for eight about half-hour after lunch, following a cameo half-century from Dale Steyn that hurt West Indies momentum.
Resuming at 289 for three, South Africa lost four wickets in the morning session to be 369 for seven at lunch, as West Indies struck telling blows to limit the hosts.
Captain Hashim Amla, starting the day on 23, looked ominous when he hammered two boundaries on either side of the wicket in the first over of the day from pacer Jerome Taylor.
However, he departed in the fourth over, lbw to fast bowler Jason Holder to one that nipped back and caught him in front.
AB de Villiers followed in the next over from Taylor, adding just one to his overnight nine before losing his off-stump to one that seamed away as the batsman looked to play to leg.
Debutant Temba Bavuma (10) and Stiaan van Zyl (29) fell cheaply to catches at the wicket to leave South Africa stumbling at 348 for seven before Steyn arrived to change the course of the innings.
He smashed a 28-ball 58, which included six fours and five sixes, in a 69-run, eighth-wicket stand with Vernon Philander, who was unbeaten on 13 at the end.
Steyn tore into Taylor, smashing the seamer for two sixes and a four in his 29th over which went for 16 and also took a turn in left-arm spinner Sulieman Benn, exacting another 16 runs before holing out to Holder in the deep off the last ball, to trigger the declaration about half-hour before tea.
Seamers Kenroy Peters (2-69), Shannon Gabriel (2-80) and Taylor (2-114) all picked up two wickets apiece.
Brathwaite and Smith then handed West Indies a steady start, posting 55 for the first wicket, as they easily negotiated the new ball burst from Steyn and Philander.
Both batsmen played with assurance against the South Africa new ball attack, gathering boundaries with some sweetly timed drives.
Brathwaite opened his account with a push to the cover boundary off Philander in the second over before taking two successive boundaries off the same bowler’s fifth over – the first a delightful straight drive and the second a cover drive off the back foot.
Smith got in on the act, twice producing flowing cover drives off Morkel, as West Indies cantered along merrily.
The left-handed Smith had faced 46 balls and struck five fours in 1 1/4 hours at the crease, when he edged Morkel to second slip where Amla held the chance on the second attempt.
Off the very next ball, Leon Johnson sparred unnecessarily at a full length delivery, steering a simple catch to Faf du Plessis at third slip.
Crawling to tea on 59 for two with Brathwaite on 37 and Samuels yet to score, West Indies defied the odds to flourish after the break and dominate the final session.
The 22-year-old Brathwaite signalled his intentions from as early as the fourth over after the break, twice spanking Steyn to the point boundary, to raise his half-century.
On four at the time, Samuels then took over with a lovely exhibition of stroke-play, especially against the leg-spin of Imran Tahir.
Getting off the mark with a streaky boundary through gully off Steyn, Samuels quickly took command. He used his feet against Tahir to gather boundaries in successive overs, clearing mid-off in the bowler’s sixth over before lofting him to the mid-wicket boundary.
He moved into the 30s with an off-driven boundary off Tahir and a few overs later, dissected square cover with precision for his sixth four off the same bowler, to ease into the 40s.
When Steyn returned for a final spell late in the day, he greeted the ace bowler with a scintillating cover drive for four and reached his 21st Test half-century in the next over from Tahir with a single to point.
West Indies nearly squandered their advantage, however, when Brathwaite drove a return catch to Tahir on 64, but the bowler failed to hold on to a difficult chance.
SOUTH AFRICA 1st innings
(overnight 289 for three)
D Elgar c wkp Ramdin b Peters 121
A Petersen c Johnson b Gabriel 17
F du Plessis c wkp Ramdin b Taylor 103
*H Amla lbw b Holder 33
+AB de Villiers b Taylor 10
T Bazuma c wkp Ramdin b Gabriel 10
S van Zyl c wkp Ramdin b Peters 29
V Philander not out 13
D Steyn c Holder b Benn 58
Extras (b4, lb5, w6, nb8) 23
TOTAL (8 wkts decl, 122 overs) 417
Did not bat: M Morkel, Imran Tahir.
Fall of wickets: 1-47, 2-226, 3-274, 4-300, 5-304, 6-325, 7-328, 8-417.
Bowling: Taylor 30-7-114-2 (w2, nb2), Peters 20-7-69-2, Holder 22-7-43-1 (nb1), Gabriel 21-0-80-2 (nb4), Benn 28-4-102-0 (nb1), Samuels 1-1-0-0.
WEST INDIES 1st innings
K Brathwaite not out 65
D Smith c Amla b Morkel 22
L Johnson c du Plessis b Morkel 0
M Samuels not out 60
TOTAL (2 wkts; 44 overs) 147
To bat: S Chanderpaul, *+D Ramdin, J Holder, J Taylor, S Benn, S Gabriel, K Peters.
Fall of wickets: 1-55, 2-55.
Bowling: Steyn 9-2-36-0, Philander 11-2-30-0, Morkel 8-1-24-2, Imran Tahir 15-1-52-0, Elgar 1-0-5-0.
Position: West Indies trail by 270 runs with seven wickets intact.
Toss: West Indies.
Umpires: B Bowden, P Reiffel; TV – Aleem Dar.