Bridgend-born Reffell, a former Wales Under-20s captain, is rewarded for a succession of outstanding displays during Tigers’ Gallagher Premiership title push this term.
He is joined by uncapped Cardiff number eight James Ratti in a 33-man group for three Tests against the world champion Springboks in July.
Elsewhere, Ospreys back George North is recalled 14 months after his last Test match appearance because of a serious knee injury, with 150-times-capped lock Alun Wyn Jones also chosen, but experienced Scarlets centre Jonathan Davies and Bristol fly-half Callum Sheedy have been left out.
Despite the presence of Jones, who was Wales’ 2019 World Cup skipper and led them to the Six Nations title last year, fly-half Dan Biggar remains as skipper.
Biggar took over leadership duties for this season’s Six Nations while Jones continued his recovery from a long-term shoulder problem.
The 36-year-old lock returned to Wales action against Italy in March, but he has only played four games since undergoing two operations to rectify an injury he suffered seven months ago.
Biggar, meanwhile, will lead a squad shorn of several injured players, with that list of absentees including Leigh Halfpenny, Johnny McNicholl, Ross Moriarty, Justin Tipuric and Aaron Wainwright.
Highly-rated Ospreys flanker Jac Morgan also misses out, but players brought back into the fold by Wales head coach Wayne Pivac include Scarlets fly-half Rhys Patchell and Ospreys flanker Dan Lydiate.
Lydiate, who has won 65 caps, has not featured for Wales since the opening game of last year’s Six Nations against Ireland, when he suffered a knee injury.
Wales face Tests in Pretoria, Bloemfontein and Cape Town, starting on July 2, having lost all 10 previous games against the Springboks in South Africa.
And Wales’ poor run since being crowned 2021 Six Nations champions has seen them win just four of 12 matches, ramping up the pressure on Pivac as he prepares for a demanding tour.
Pivac said: “I spoke to Tommy Reffell before we announced the squad for the Six Nations. We looked hard at Tommy and decided to leave him out then.
“He has played very well since, he’s been very consistent – one of the most consistent players in the English Premiership – so we feel that he deserves an opportunity and he will be well tested on this tour.”
On the captaincy, Pivac added: “We’ve obviously got great leadership in the group with Alun Wyn and Dan. Dan did well in the Six Nations and Al has come back from a pretty big lay-off.
“He has had a little bit of rugby, and we want him to hit his straps as a second-row and be the best player he can be and focus on playing.”