The men's 4x100 m freestyle relay event at the 2010 South American Games was held on March 29 at 19:20.
| Standing records prior to the 2010 South American Games | ||||
|---|---|---|---|---|
| World record |  United States | 3:08.24 | Beijing, China | 11 August 2008 |
| Competition Record |  Argentina | 3:24.16 | Buenos Aires, Argentina | 18 November 2006 |
| South American record |  Brazil | 3:21.67 | Mar del Plata, Argentina | 15 April 2000 |
| Rank | Lane | Athlete | Result | Notes |
|---|---|---|---|---|
 | 5 |  Venezuela | 3:22.89 | CR |
| Albert Subirats | 50.71 | |||
| Christian Quintero | 51.35 | |||
| Daniele Tirabassi | 51.18 | |||
| Crox Acuña | 49.65 | |||
 | 4 | Brazil | 3:24.56 | |
| Nicolas Oliveira | 50.99 | |||
| Guilherme Roth | 51.62 | |||
| Rodrigo Castro | 50.83 | |||
| Thiago Pereira | 51.12 | |||
 | 6 |  Colombia | 3:26.16 | |
| Juan Cambindo | 52.60 | |||
| Daniel Cuellar | 51.84 | |||
| Julio Galofre | 51.14 | |||
| Marco González | 50.58 | |||
| 4 | 7 |  Paraguay | 3:29.62 | |
| José Enmanuel Lobo | 53.03 | |||
| Favio Persano Segovia | 54.24 | |||
| Charles Hockin | 52.21 | |||
| Ben Hockin | 50.14 | |||
| 5 | 3 | Argentina | 3:29.71 | |
| Martín Naidich | 53.09 | |||
| Federico Grabich | 50.28 | |||
| Juan Monzón | 53.10 | |||
| Gustavo Paschetta | 53.24 | |||
| 6 | 1 |  Peru | 3:32.92 | |
| Sebastián Arispe Silva | 54.22 | |||
| Emmanuel Crescimbeni | 52.36 | |||
| Manuel Alonso Yabar-Davila | 53.39 | |||
| Sebastián Jahnsen Madico | 52.95 | |||
| 7 | 2 |  Uruguay | 3:34.07 | |
| Rodrigo Cáceres | 53.14 | |||
| Nicolás Francia | 53.83 | |||
| Joel Romeu | 51.96 | |||
| Martín Kutscher | 55.14 | |||
| 8 | 8 |  Ecuador | 3:40.72 | |
| Mario Navas Navarro | 54.96 | |||
| Ivan Enderica Ochoa | 54.82 | |||
| Carlos Polit Carvajal | 55.71 | |||
| Diego Zambrano Macias | 55.23 | |||
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