The game was a step up in intensity compared to the three easy wins the Lions achieved in their opening games. The South Africa A team included 16 members of their 2019 Rugby World Cup-winning squad.
World Cup-winning coach Rassie Erasmus provided guidance running the sideline as a waterboy for the home team.
It was a blow on a day when the Lions received a boost with the news that original captain Alun Wyn Jones will join the tour along with Stuart Hogg and assistant coach Gregor Townsend.
The Lions again made late changes to their team. Dan Biggar suffered a rolled ankle at the captain's run resulting in Owen Farrell starting at first five-eighths. They also lost wing Liam Williams, another late replacement in the starting XV, when he was floored in a big hit by lock Eben Etzebeth one minute into the game.
The Lions were undone by a fast start from the South Africans who got out to a 17-3 lead by halftime.
Etzebeth led the pack well, and it was his charge-down of an attempted chip kick by Farrell that saw Damian de Allende gather the ball to send wing Sbu Nkosi away for the first try.
Soon after a Farrell penalty goal got the Lions on the board, 28 minutes into the game, wing Cheslin Kolbe fielded an exit kick from the Lions. He sauntered forward before standing up Chris Harris and Louis Rees-Zammit with his side-step to feed Lukhanyo Am for him to run in the second try.
Not even two yellow cards against Faf de Klerk and Marco van Staden could help the Lions against some steadfast South African defence.
There was a moment of potential controversy when Rees-Zammit looked to have scored, only to be penalised by referee Jaco Peyper for a double movement.
Kolbe said afterwards, "We just had to show what this jersey means to us and with what the country is going through, just to put a smile on people's faces and give hope to people out there.
"The character the boys have shown tonight was incredible. The level of intensity is a massive step up compared to the Top 14, but it is just great back on the field after a long wait since the World Cup.
Captain Lukhanyo Am said he was proud of the side, there had been a lot that had gone well, but also some areas that hadn't, and they knew where the Springboks would need to improve for the Tests.
"We're very happy with our performance. We all know there has been a drought of Test match rugby. We're excited to be back and in the mix of things. We'll go back to the drawing board and see where we can improve.
"It was a great foundation for the series ahead," he said.