In his younger days he played for Carrickfergus Cricket Club as a professional. De Villiers became the second youngest and second fastest South African to reach 1000 test runs after Graeme Pollock. In his test career so far de Villiers has batted, bowled and kept wicket as well. He is a naturally born sportsman and has talents in golf (playing off scratch despite playing infrequently), rugby, cricket and tennis. However, he chose to pursue a career in cricket and, after a spell in the South Africa U19 team, he made his debut for the Titans in 2003/4.

He made his test debut as a 20 year old on 16 December 2004 against England at Port Elizabeth. He made an impression opening the batting, but was dropped down the order for the second test and also handed the wicket-keeping gloves. In this match, he made a match saving half century from number seven. However, he found himself at the top of the order again for the final test of the series and has played the majority of his tests there. Since then he has not missed a Test match and has also batted down the order in some tests leading to speculation that he may possibly take the place of Mark Boucher as the wicket-keeper/batsman when Boucher retires. Despite a good tour of the Caribbean where he scored 178 to seal the series, his rapid progress was halted on the tour of Australia in 2005. Despite playing Shane Warne well, he struggled and made just 152 runs in 6 innings. Although he currently only holds a mediocre test record, de Villiers holds the record for scoring most Test runs without getting out for a duck.