Richard (BRAD PITT) and Susan Jones (CATE BLANCHETT) are an unhappily married couple traveling in Morocco trying to get over the recent loss of one of their kids. Unbeknownst to them, sheepherder Abdullah (MUSTAPHA RACHIDI) has recently purchased a high-powered rifle from Hassan (ABDELKADER BARA) for his boys Ahmed (SAID TARCHANI) and Yussef (BOUBKER AIT EL CAID) to protect their herd from hungry jackals.
As the Jones' tour bus ends up traveling near the family's grazing grounds, Yussef -- when not enjoying a peek at his sister, Zohra (WAHIBA SAHMI) -- decides to test the rifle's range, resulting in Susan accidentally being shot and badly wounded. Desperate to get her help, Richard has the bus divert to a nearby village where he tries to get help from the far-off American embassy.
At the same time, Mexican immigrant Amelia (ADRIANA BARRAZA) is a housekeeper and nanny in San Diego caring for siblings Debbie (ELI FANNING) and Mike (NATHAN GAMBLE). Her son is getting married south of the border, and unable to find anyone to baby-sit the kids, she and her reckless nephew Santiago (GAEL GARCÍA BERNAL) drive them into Mexico for the festivities, unaware of the difficulties they'll face getting back.
Meanwhile, Chieko (RINKO KIKUCHI) is a Japanese teen who enjoys hanging out with her friends, but feels isolated not only by being deaf, but also by the recent death of her mother that's left her father, Yasujiro (KÔJI YAKUSHO), emotionally distant and often not home.
With that single shot from Yussef's rifle, all of their lives become intertwined and forever affected by that act of violence.