Captain Smith scored 132 and Herschelle Gibbs, Jacques Kallis and Martin van Jaarsveld cracked half centuries as the hosts completely dominated the opening day of the four-match series.
Smith was at the crease for more than four hours, facing 184 balls and hitting 22 fours as he passed 1,500 runs in Tests.
Gibbs, who scored 60, and Smith added 149 for the first wicket, a record for South Africa against West Indies.
Kallis was 87 not out at the close with Van Jaarsveld on 69, his maiden test half-century, the pair sharing an unbroken fourth-wicket stand of 128.
Smith and Gibbs dominated a West Indian attack that wilted on an intensely hot day.
None of the bowlers posed a threat to the batsmen in the morning session. They wasted the new ball by bowling on both sides of the wicket, and the only appeal of the first session came in the second hour when fast bowler Corey Collymore struck Gibbs on the pads.
However, Hair erred an hour after a lunch when he failed to spot that Collymore overstepped in delivering the ball that bowled Gibbs through the gate.
Gibbs faced 103 balls and hit eight fours and a six in what was, by his normally aggressive standards, a solid but subdued innings.
South Africa lost their second wicket three overs later when Jacques Rudolph, who struggled to settle at the crease, edged a ball from fast bowler Vasbert Drakes to be neatly caught by Brian Lara at slip for two.
Smith went to his century with an on-drive for two off Mervyn Dillon 20 minutes before tea but was nearly dismissed with the last ball of the second session, Lara, at leg slip, failing to hold a sharp chance off part-time leg spinner Ramnaresh Sarwan.
Smith was out after tea when he slashed a ball from Fidel Edwards to Lara at first slip.
West Indian opener Chris Gayle left the field after lunch after injuring a hamstring chasing a ball in the deep.
Scoreboard
SOUTH AFRICA (1st innings)
G.Smith c Lara b Edwards 132
H.Gibbs b Collymore 60
J.Rudolph c Lara b Drakes 2
J.Kallis not out 87
M.van Jaarsveld not out 69
EXTRAS (lb-5 nb-9 w-4) 18
TOTAL (for three wkts, 90 overs) 368
FALL OF WKTS: 1-149 2-160 3-240
DID NOT BAT: N McKenzie, M Boucher, S Pollock, R Peterson, A Nel, M Ntini.
BOWLING: Edwards 19-2-78-1 (w3), Dillon 20-3-55-0 (nb4), Collymore 17-1-88-1, Drakes 19-2-70-1 (nb5), Ganga 4-0-26-0, Sarwan 2-0-7-0, Hinds 9-2-39-0 (w1)
WEST INDIES:<\B> C.Gayle, W.Hinds, R.Sarwan, B.Lara, S.Chanderpaul, D.Ganga, R.Jacobs, V.Drakes, M.Dillon, C. Collymore, F.Edwards—Reuters