Rapinoe grew up in Redding, California with her parents, Jim and Denise, and five siblings, including her fraternal twin, Rachael Rapinoe. Denise and Jim raised seven children together, not all their own. Denise has a son and daughter, Michael and Jenny, from a previous marriage; then came older brother Brian and then the twins five years later. Jim and her grandfather Jack both served in the Army. She has Italian (from her paternal grandfather) and Irish ancestry. She idolized her older brother Brian and started playing soccer at age three after watching him play the sport, but he started using drugs when the girls were in second grade. When she was ten and he was fifteen, he was put in juvenile detention, and was thereafter in and out of various prisons including the super-max Pelican Bay State Prison. Brian has since made a determined effort to avoid drugs after seeing his younger sister's success in international soccer and not being able to be present with his family. For both Rachael and Megan, soccer was a means to get away from the drug abuse that is widespread in rural California.
Rapinoe spent most of her youth playing with teams coached by her father until high school. Instead of playing soccer at , Rapinoe played for the Elk Grove Pride club team, located south of Sacramento. She competed in track as a freshman and sophomore; competed in basketball as a freshman, sophomore, and senior; and was on the honor roll every semester of high school. Rapinoe was named Parade and National Soccer Coaches Association of America (NSCAA) All-American as a junior and senior. She was named to McDonald's All-American Girls High School Soccer West Team in 2004. Rapinoe played for the under-14 Northern California state Olympic Development Program (ODP) team in 1999, as well as the regional ODP team in 2002.
Elk Grove United, 2002–2005
From 2002 to 2005, Rapinoe played for Elk Grove Pride in the Women's Premier Soccer League (WPSL) along with her sister, Rachael, and future national teammate, Stephanie Cox. She and her family commuted two-and-a-half hours from her hometown to play with the team. During the US Youth Soccer National Championships, she scored an equalizer goal in the 18th minute to tie the game 1–1 against the Peachtree City Lazers. Elk Grove United finished second at the nationals after the Lazers scored a game-winning goal in the second half.
University of Portland Pilots, 2005–2008
Rapinoe and her sister both attended the University of Portland in Portland, Oregon. The Rapinoe twins almost committed to Santa Clara University before choosing to play for the Portland Pilots on full scholarships. Rapinoe played in the 2004 FIFA U-19 Women's World Championship in 2004, where the United States finished third. The result was that she did not play college soccer in that year.
In 2005, as a freshman, Rapinoe helped the Pilots to an undefeated season and the NCAA Division I Women's Soccer Championship. During the College Cup quarterfinal against Notre Dame, she scored twice and served one assist, helping the Pilots win 3–1 and advance in the College Cup. During the College Cup final against UCLA, she scored one goal and served an assist helping the Pilots win 4–0. She was named NSCAA First Team All-American and was on the Soccer America First Team Freshman All-America. Rapinoe made the NCAA Women's Soccer Championship All Tournament Team and was the West Coast Conference Freshman of the Year. She was also named to the All-West Coast Conference First Team and the All-West Coast Conference Freshman Team. Rapinoe played and started all 25 games as an attacking midfielder, scoring 15 goals and adding 13 assists for 43 points – ranking fifth for freshman point totals in the school's history. That year, she also scored seven game-winning goals.
"I know this sounds weird, but getting hurt was one of the best things that ever happened to me. It really gave me a different perspective. Before, everything was going how it was supposed to be and I wasn't really appreciative of what I was doing and what it took to be there. The injury grounded me in a lot of different ways. The rehab process makes you stronger on all fronts, mentally and physically. I feel stronger and a better person for it. I would never wish it on anyone, but I don't wish I could take it back."
As a sophomore in 2006, Rapinoe was among the nation's leading scorers with ten goals and two assists in eleven matches. During a match against Washington State University on October 5, she suffered her first season-ending anterior cruciate ligament injury (ACL) injury. Despite her injury, she was one of four Portland players in the program's history, including Christine Sinclair, Tiffeny Milbrett, and Shannon MacMillan, to score 25 goals and 15 assists in two seasons. In 2007, Rapinoe suffered her second season-ending ACL injury two games into the season. She was granted a medical hardship waiver by the National Collegiate Athletic Association (NCAA) but did not use it.
After taking her time to recover from her second ACL injury, Rapinoe returned for the 2008 season and was on the starting lineup in all 22 games for the Pilots. She helped the team secure a 20–2 record scoring five goals and serving 13 assists. Her 13 assists ranked first for the Pilots as well as in the West Coast Conference and she was named West Coast Conference Player of the Year. She was also named a Soccer America First-Team All-American and NSCAA Second Team All-American. Although she had one more season of college eligibility remaining due to her NCAA medical hardship waiver, she opted to enter the Women's Professional Soccer Draft instead. Rapinoe's 88-point career, including 30 goals and 28 assists, ranks tenth in the school's history despite her playing only 60 games.