Pretorius, born in Nelspruit, qualifies on residency for Wales and became available for selection last month.
He is joined in the squad by his Blues back-row colleague Josh Navidi, Ospreys wing Eli Walker and lock James King, plus Newport Gwent Dragons second-row forward Andrew Coombs.
Wales have been particularly badly hit in the second-row department, with Alun-Wyn Jones, Luke Charteris and Bradley Davies currently unavailable to Howley and not named in his initial Six Nations squad.
There are recalls for Clermont Auvergne full-back Lee Byrne, who has not featured in a Wales matchday 23 since the 2011 World Cup, and Exeter prop Craig Mitchell.
Star prop Adam Jones also returns after missing the entire autumn Test series this season because of injury and Howley will hope that some of his other injured contingent, including Dragons flanker Dan Lydiate, can play some part in the tournament.
Pretorius apart, there are few surprises with the uncapped contingent.
Walker and Australia-born King have both been in outstanding form for the Ospreys, as has Coombs in Dragons colours and former Wales Under-20 captain Navidi for the Blues.
King has English parents, but he was initially brought up in north Wales and played for Mold Rugby Club.
Howley said: "We have put together a very experienced squad and complimented that by rewarding the in-form players with a call-up.
"The players in the squad have been playing really well, and we have been pleased with their individual performances.
"We have a group of players who know how to win big matches and have experienced success. We are adding to that players who have stood out and performed well for the regions this season."
Wales squad for the RBS 6 Nations Championship:
Backs: L Byrne (Clermont Auvergne), Liam Williams (Scarlets), L Halfpenny (Cardiff Blues), E Walker (Ospreys), G North (Scarlets), A Cuthbert (Cardiff Blues), S Williams (Scarlets), J Roberts (Cardiff Blues), J Davies (Scarlets), J Hook ( Perpignan), D Biggar (Ospreys), M Phillips ( Bayonne), T Knoyle (Scarlets), Lloyd Williams (Cardiff Blues).
Forwards: S Andrews (Cardiff Blues), C Mitchell (Exeter), A Jones (Ospreys) P James (Bath), G Jenkins ( Toulon), R Bevington (Ospreys), R Hibbard (Ospreys), K Owens (Scarlets), M Rees (Scarlets), R Jones (Ospreys) L Reed (Blues), I Evans (Ospreys), J King (Ospreys), A Coombs (Newport Gwent Dragons), J Turnbull (Scarlets), J Navidi (Cardiff Blues), A Shingler (Scarlets), J Tipuric (Ospreys), S Warburton (Cardiff Blues, capt) T Faletau (Newport Gwent Dragons), A Pretorius (Cardiff Blues).