South Africa were 254 for four at the close Friday in reply to Pakistan's first innings total of 313.
But Prince shared the limelight with Pakistan seamer Mohammad Asif who took all four wickets for 58 runs.
The 24-year-old Asif was playing his first Test since having a doping ban overturned.
The left-handed Prince, who topped the averages in the recent series against India, was unbeaten on 77. He came in with South Africa in trouble at 53 for three and shared stands of 90 with Hashim Amla (71) and an unbeaten 111 with Herschelle Gibbs (58 not out).
Makhaya Ntini was mainly responsible for Pakistan failing to get the total in excess of 350 they had hoped for.
Ntini took five for 83, his 16th five-wicket haul in Tests, as Pakistan paid a heavy penalty for their obsession with hook and pull shots which claimed seven batsmen.
Pakistan self-destructed in a frenetic morning's play, scoring 71 runs in 67 minutes and 12.5 overs but losing five wickets.
Three wickets fell to hook shots on the first day and the trend continued Friday, with captain Inzamam-ul-Haq the first offender.
Inzamam was out for 42 in the fourth over of the day when he hooked Ntini straight to Amla on the square leg boundary. He stood at the crease looking disgusted with himself before trudging slowly to the dressing room.
Kamran Akmal, who made an aggressive 29, top-edged a pull to mid-on off Andre Nel and Shahid Nazir, who could have been out several times in a hit-or-miss innings of 15, top-edged an attempted hook off Ntini to gully.
Immediately after Nazir's dismissal Rana Naved-ul-Hasan hooked Ntini high to square leg and Amla took a spectacular diving catch but landed over the boundary for the batsman to score six runs.
Danish Kaneria fell to a routine catch at second slip as Ntini took his fifth wicket before Naved-ul-Hasan was the seventh man to be out hooking or pulling, top-edging a pull for Nel to hold a catch off his own bowling.
The tall Asif swung the ball both ways when South Africa started their innings.
South African captain Graeme Smith, who finished the recent series against India with three successive half-centuries, was out without scoring when he edged a ball that swung away from the left-hander to wicketkeeper Akmal.
De Villiers followed in Asif's next over when he edged an out-swinger to Younis Khan at second slip.
South Africa could have been in worse trouble if Amla had been caught on four when Yasir Hameed could not hold a sharp chance at gully off Asif.
Jacques Kallis made 18 before he was Asif's third victim, caught at second slip, but Amla and Prince steadied the innings.
Amla was looking in authoritative form as he made his 71 off 152 balls with 11 fours before edging a catch to Akmal when he pushed forward outside his off stump.
While Prince played a chanceless innings, Gibbs showed his best touch of the summer as Pakistan's bowlers looked ineffectual.
By the close Prince had faced 144 balls and hit 10 fours while Gibbs had faced 109 and hit 11 boundaries.
Pakistan 313 (Younis 68, Yasir 65, Inzamam 42; Ntini 5 for 83, Nel 3 for 100) Vs South Africa 254 for 4 ( Ashwell Prince 77 n o, Hashim Amla 71, Herschelle Gibbs 58 n o; Mohd Asif 4 for 58)