Reyna Grande was born in the city of Iguala in the southern Mexican state of Guerrero. She is the youngest of three siblings born in Mexico and has a brother and sister born in the U.S. Her childhood home was a shack made of bamboo sticks with tar-covered cardboard for a roof. When Grande was four years old, her parents moved to the United States, leaving her to be raised by her grandparents. When she was nine years old, her father returned and brought the three siblings across the U.S.-Mexico border into California.

Grande grew up in the predominantly Latino Los Angeles neighborhood of Highland Park. In 1999 Grande became the first person in her family to receive a college diploma when she graduated from the University of California, Santa Cruz, with majors in creative writing and film and video. In 2003 she was chosen to be a PEN USA Emerging Voices Fellow and went on to obtain an M.F.A from Antioch University. Her debut novel, Across a Hundred Mountains, is published by Atria Books, a division of Simon and Schuster. For this novel, Grande was awarded the 2006 Premio Atzlan Literary Award and a 2007 American Book Award. Grande's second novel,Dancing with Butterflies, was published in October 2009 by Washington Square Press. It received a first prize 2010 International Latino Book Award in the category of Women's Issues Books.

In addition to her writing, Grande is a sought-after speaker at middle and high schools, colleges and universities across the nation. She also moderates a book club, teaches creative writing workshops, and is the program director for the Los Angeles Latino Book and Family Festival.