The home side fell behind after two minutes when Mosa Lebusa scored for the relegation-threatened visitors in the penultimate-round match.
But goals from Zimbabwean Khama Billiat, Brazilian Ricardo Nascimento and Sibusiso Vilakazi before half-time turned the tide in favour of the 2016 CAF Champions League winners.
Second-place Orlando Pirates fell 1-0 at Cape Town City, leaving Sundowns with an unassailable seven-point advantage going into the final round on May 12.
Sundowns coach Pitso Mosimane was relieved more than ecstatic after his multi-national team won a third Premiership title in five seasons.
"It has been a tough, long haul and my players have made a lot of sacrifices," said the 53-year-old former South Africa striker and coach.
"We have been averaging two matches a week, meaning many nights in hotels away from our families and friends, but we never wavered.
"When Ajax snatched an early lead I never doubted that we would hit back hard. Mentally, this Sundowns side is extremely strong."
Mosimane and his stars now turn their attention to the Champions League, with their first group game at home next Friday against title-holders Wydad Casablanca of Morocco.
A goal by "bad boy" Ayanda Patosi on 35 minutes gave fifth-place Cape Town City victory over Pirates, who are guaranteed to finish runners-up.
Patosi has battled discipline and weight problems since quitting Belgium last year and returning home.
Kaizer Chiefs put recent troubles behind them to defeat Maritzburg United 2-0 and replace them in third place.
Goals by Venezuelan Gustavo Paez and Dumisani Zuma secured three points for Chiefs, whose coach Steve Komphela quit last weekend after an FA Cup semi-final loss triggered crowd violence.
It was the first victory for caretaker coach and former Malawi star Patrick Mabedi,who had assisted Komphela, after a midweek loss at Golden Arrows.
With Platinum Stars already relegated, there is a four-club struggle to avoid finishing second last and going into play-offs with two second-division sides for one Premiership spot.
An Ajax team coached by Turk Muhsin Ertugral are in gravest danger with 31 points ahead of a final-round fixture at home to Chiefs.
But three-time Premiership title-holders SuperSport United, Polokwane City (both 33 points) and Baroka (34) could also finish second last.