Santa Cruz, who was on loan at La Liga side Real Betis last season, passed a medical earlier in the day.
Onyewu has played for a number of clubs in Europe including Standard Liege, Newcastle United, Inter Milan and Twente.
The 30-year-old central defender is Malaga's fourth signing in the last 24 hours after they also landed Argentine striker Javier Saviola and Chile midfielder Manuel Iturra.
Qatari-owned Malaga have been drawn in Champions League Group C along with AC Milan, Zenit St Petersburg and Anderlecht in their first venture into Europe's elite club competition.
- Real Betis
- La Liga
- Standard Liege
- Inter Milan
- Newcastle United