His first outing was a rough occasion as it lasted less than 10 minutes after the midfielder suffered a serious knee injury against France in Marseille and spent nine months out of the game.
A shoulder injury in a warm-up match ahead of the 2003 World Cup stuffed his comeback before it got off the ground and he didn't play his second test until he ran out against the Pacific Islanders in Gosford in Australia in July, 2004.
"It has been a long road," he said of his test career. "And certainly there were definitely times when I didn't think I would get to number two."
But de Villiers eventually collected his second cap and began to forge a lengthy test career and he will make his 100th appearance for South Africa when the Springboks meet the All Blacks in Wellington on Saturday night.
"Certainly you do test your character and I went through a lot of hard times but I believe I got through it stronger and never imagined that I would get to 100."
The 33-year-old will captain the visitors this weekend, while his wife and father will also be in attendance to mark the milestone.
He will become only the fifth South African to join the 100-club, alongside teammates Victor Matfield and Bryan Habana, while retired warhorses John Smit and Percy Montgomery also achieved the feat.
Known for snatching intercept tries earlier in his career, de Villiers made his 50th test appearance against the All Blacks and said he had developed a respectful rivalry with long-time New Zealand midfielders Ma'a Nonu and Conrad Smith.
"It is nice to play against them and for the old battle to continue and hopefully we can just have a drink afterwards and celebrate my 100th game," de Villiers said.
Of the many highlights from his career, de Villiers spoke highly of the test victories over the All Blacks, notably South Africa's 2005 win that came at his homeground in Cape Town and the 2009 victory in Hamilton that secured South Africa the Tri Nations crown.
"Being a bit of a purist, when it comes to rugby, I think that's the ultimate challenge for me was to always play against the All Blacks."
South Africa are coming off a 24-23 loss to Australia in Perth last Saturday and de Villiers said it would be a tough ask to beat the Rugby Championship-leading All Blacks this weekend.
"You're up against a team that's been playing consistently really well so you can't expect them to have an off-day and you be lucky and get a win. You're going to have to play well, you're going to have to prepare well and you're going to have to execute on the day."
- By Daniel Richardson of APNZ