Kirsten made his Test debut against Australia in Melbourne in 1993. He retired from international cricket in 2004 after crafting a match-winning 76 in his final innings, against New Zealand. Against the same country he had made history by becoming the first-ever Protea to play in 100 Test matches.

Over the years, he gained a reputation as being a sturdy batsman in both Test cricket and One Day cricket. He could up the tempo of an innings if he needed to, but more often than not he simply waited for the bad ball, much like Steve Waugh and Justin Langer. He was also a reliable fielder. Kirsten held the South African records for most runs and centuries in a Test career, before both were surpassed by Jacques Kallis. He was the first Test batsman to make hundreds against each of the other 9 Test nations. He scored 275 runs against England as a result of batting for over 14 and a half hours as South Africa followed on at Kingsmead in Durban, it still stands as the second-longest innings (in terms of duration) in Test history. The high score was later surpassed by Graeme Smith when he made 277 against England in 2003. He still holds the record for highest innings by a South African in a One Day International; 188 not-out made against the United Arab Emirates during the 1996 World Cup, which is the tenth highest innings of all time in One Day International cricket, and the highest score in World Cup cricket history. This record stood until it was surpassed by Chris Gayle who scored 215 against Zimbabwe in 2015. Later, that record was surpassed by Martin Guptill who scored 237* against the West Indies in the quarter finals of that very World Cup.