There were few surprises from coach Hugo Broos as he largely stuck with the players who earned a first appearance at the global finals for Bafana Bafana in 16 years.
South Africa face co-hosts Mexico in the tournament opener on June 11, before Group A clashes with Czech Republic in Atlanta (June 18) and South Korea in Monterrey (June 24).
Centre-back Makhanya, 22, plays for Philadelphia Union in Major League Soccer, while Cross, 25, once in the academy at Newcastle United, is a left-back for local Soweto side Kaizer Chiefs.
Both had not been involved in qualifying, but a desire to have more defensive options led to their selection. Regular left-back Aubrey Modiba has also been selected despite missing Sunday's second leg of the CAF Champions League final for Mamelodi Sundowns with a hamstring injury.
Burnley striker Lyle Foster will lead the line and Zwane's experience and guile on the ball is seen by Broos as vital to the team, with 19 of the 26 players based in the South African league.
Thapelo Morena likely would have made the cut but misses out with injury, while Patrick Maswanganyi did not make it despite helping Orlando Pirates in their first domestic championship in 14 years.
The World Cup is a swansong to coaching for their Belgian tactician Broos, 74, who has already said he will call time on his career after the finals.
The former defender quit international football as a player after the 1986 World Cup that was also hosted in Mexico, where he helped Belgium to fourth place.
“I know those players who had to drop out will be very disappointed tonight,” Broos said. “There were some very difficult decisions to be made. I hope I have chosen the right ones.”
South Africa have appeared in three previous World Cup finals having debuted in 1998. They qualified again in 2002 and hosted the tournament in 2010. They exited in the group stages on each occasion.
Squad:
Goalkeepers: Ronwen Williams (Mamelodi Sundowns), Ricardo Goss (Siwelele), Sipho Chaine (Orlando Pirates)
Defenders: Khuliso Mudau, Aubrey Modiba, Khulumani Ndamane (all Mamelodi Sundowns), Olwethu Makhanya (Philadelphia Union, USA), Bradley Cross (Kaizer Chiefs), Thabang Matuludi (Polokwane City), Nkosinathi Sibisi, Kamogelo Sebelebele (both Orlando Pirates), Ime Okon (Hannover 96, Germany), Samukele Kabini (Molde FK, Norway), Mbekezeli Mbokazi (Chicago Fire, USA)
Midfielders: Teboho Mokoena, Jayden Adams (both Mamelodi Sundowns), Thalente Mbatha (Orlando Pirates), Sphephelo Sithole (Tondela, Portugal)
Forwards: Oswin Appollis, Tshepang Moremi, Evidence Makgopa, Relebohile Mofokeng (all Orlando Pirates), Lyle Foster (Burnley, England), Iqraam Rayners, Themba Zwane (both Mamelodi Sundowns), Thapelo Maseko (AEL Limassol, Cyprus)
Fixtures:
11 June, 21:00 CET: Mexico vs South Africa – Mexico City Stadium
18 June, 21:00 CET: Czech Republic vs South Africa – Atlanta Stadium
25 June, 03:00 CET: South Africa vs South Korea – Monterrey Stadium