Steyn, currently the world's number one ranked Test bowler, joined West Indian Malcolm Marshall and New Zealand's Richard Hadlee in taking 300 wickets in 61 matches.
"It's an unbelievable achievement," said South African captain Graeme Smith before the match.
"He's our go-to guy. He's got there really quickly. He always seems to make an impact for us. He's the type of guy as a captain he's an asset to have. You can throw him the ball and you know he'll make a play for you somewhere during the Test match.
"When he gets that bit between his teeth you really start to see things happening."
Steyn had to wait until the third ball of his second spell to take his first wicket of the match and was overshadowed by new ball partner Vernon Philander who took the first five wickets at a cost of four runs.
Steyn's strike reduced the tourists to 31 for seven after they won the toss.