Like in Sunday's (AEST) win over the Sharks, Warren Gatland's team was defensively vulnerable in the first half on Thursday and was duly punished by a South Africa A team littered with 2019 Rugby World Cup winners.
Indeed, two of those world champions scored South Africa A's tries, with Sbu Nkosi and Lukhanyo Am going over.
Wyn Jones' score early in the second half brought the Lions back into it, but they were unable to stop a seven-match unbeaten streak – their longest such run since a trail of 10 wins across the 1989 and 1993 tours – coming to an end.
South Africa A started as they meant to go on in the first half – Nkosi seeing what seemed a certain try denied by Anthony Watson, though Morne Steyn, who converted the decisive points in the Lions' 2009 series against the Springboks, then nosed the home team ahead with a penalty.
Nkosi got his try in the 12th minute, however, with the wing bursting down the field to dive over in the corner after Eben Etzebeth charged down Owen Farrell's kick.
Steyn added the extras and, after Farrell had hit a three-pointer for the tourists, the 37-year-old was on point with the boot again in the 33rd minute, this time converting Am's try.
Yellow cards for Faf de Klerk and Marco van Staden reduced South Africa A to 13 men before the interval, and the Lions made their numerical advantage count when Wyn Jones barged over four minutes after the restart.
It was Jones' last act, with the Wales international taken off as a precaution – Gatland having already lost Liam Williams to a head injury in the first half.
Farrell hit another penalty to further reduce the deficit, though Louis Rees-Zammit saw a try disallowed by TMO and then Steyn's perfect record was dashed when he punted a long-range effort wide.
Steyn also squandered a drop-goal attempt late on, yet the Lions failed to make him pay as they were dealt a first setback of their 2021 tour.