Holder, who hit an unbeaten 54 from 88 deliveries, watched on as the Proteas built a commanding advantage and were left 223-5 in their second innings.
Opener Aiden Markram (51) and Kyle Verreynne (50) starred for South Africa, with no repeat of the opening day carnage that saw 17 wickets fall for either side.
The Proteas were bowled out for 160 in their first innings, with Holder's half-century steadying the ship after the Windies had wobbled to just 97-7 in the 28th over.
With a 16-run advantage heading into the second innings, Markram and Tony de Zorzi put together a 79-run opening partnership before the latter was caught for 39.
The dismissal of Markram saw the visitors lose three wickets for 19 runs, but Verreynne and Wiaan Mulder (34 not out) were able to put together an 84-run sixth-wicket stand.
South Africa will resume with Verreynne and Mulder on day three, but Holder remains positive that his side can produce a comeback.
“I was just trying to eke out as many runs as we could,” said Holder at the end of the day. “First session tomorrow is obviously crucial for us.
"The most important thing is not to let the runs get too far away, let them sweat a little bit more for their runs, and I believe, with the amount of time left in the game, that we can chase anything they give us.”
Seales, who finished with nine wickets in a 40-run loss that helped South Africa win the ICC World Test Championship series 1-0, achieved the milestone move, which now makes him the top-ranked Test bowler from the West Indies.
The 22-year-old Trinidadian, who has enjoyed fairly good form since his return from injury, surpassed Barbadian seamer Kemar Roach, who slipped one place down to 18th, as his journey to fitness continues.
Spinners Jomel Warrican (52nd) and Gudakesh Motie (64th), both moved two spots up, while fast bowler Shamar Joseph also progressed 11 spots to 54th in other significant movements for the West Indies players in the bowling rankings.
South Africa’s Player of the Match Wiaan Mulder advanced 27 places to 65th position after finishing with six wickets, while off-spinner Dane Piedt is up nine places to 66th after claiming two West Indies wickets in the second innings of the match.
In the Test batting rankings, former West Indies captain Jason Holder is up seven places to 60th position following his unbeaten knock of 54 in the first innings. He is also up two places to fifth in the list of all-rounders.
South Africa opener Aiden Markram and wicketkeeper Kyle Verreynne have gained after notching half-centuries in the second innings. Markram inched up two places to 21st, while Verreynne has progressed from 62nd to 46th.
In the ICC World Test Championship, West Indies are last in the nine-team championship with 18.52 after nine matches, while South Africa are in fifth place with 38.89 percentage points after six matches.
India lead the table with 68.52 percentage points after nine matches, with Australia in second on 62.50 after 12 outings. New Zealand and Sri Lanka are the other teams ahead of South Africa.
Meanwhile, in the ICC Men’s ODI Batting Rankings, Scott Edwards of the Netherlands has moved up six places to 26th position after scores of 72 and 65 against Canada and the United States, respectively, in the ICC Men’s Cricket World Cup League 2.
Aaron Jones of the United States (up 11 places to 56th) and Vikramjit Singh of the Netherlands (up nine places to 79th) are others to move up the batting rankings, while Aryan Dutt of the Netherlands is up five places to 33rd.
