[2][3] Mewis grew up in Hanson, Massachusetts, where she attended Whitman-Hanson Regional High School and played on the soccer team.

[4][5] As a freshman at Boston College, Mewis recorded five goals and six assists, and was second on the team in shots taken with 72, bettered only by fellow Eagle and United States U-17 teammate, Vicki DiMartino.

[4] During her sophomore year in 2010, Mewis started all 25 games on the season and led the Atlantic Coast Conference (ACC) in shots with 101.

After opening the season with a nine-game scoring streak, second to her personal and program record of 11 games which she accomplished in 2010, she was named a Division 1 ECAC All-Star and Hermann Trophy Semifinalist.

[7][8][9][10] She made her first appearance for the club during a 5–0 win against the Western Sydney Wanderers FC on January 8 and scored the team's fifth goal in the 89th minute of the match.

[11][12] Her second and final appearance occurred on January 12 when the team was defeated 5–1 by eventual regular season champions, Brisbane Roar FC.

[19] Mewis made 20 starts as a rookie for FC Kansas City during the regular season helping the team finish second in the standings with an 11–5–6 record.

[23] Of the trade, Reign FC coach, Laura Harvey said, "Kristie is a young, bright and talented player who we feel can benefit our long-term plan.

"[24] On November 18, 2013, she was traded alongside Michelle Betos and two 2015 NWSL College Draft picks to the Boston Breakers for Sydney Leroux.

October 2014 Mewis signed a three-month contract with Iga FC Kunoichi of the Japanese Nadeshiko League first division.

Mewis returned stronger in 2019 with a new mindset stating: "Me tearing my ACL was kind of a blessing in disguise because I feel like it just woke me up a little bit.

[37] She made her debut for the club on January 21, 2024, coming on as a substitute for Honoka Hayashi in the 62nd minute, assisting a goal in the 4–3 loss against Tottenham Hotspur.

[38] Mewis co-captained the United States U-17 team that was runner-up at the inaugural 2008 FIFA U-17 Women's World Cup in New Zealand.

In January 2013, Mewis was called to the national training camp by head coach Tom Sermanni in preparation for a friendly match against Scotland.

[42] Mewis scored the game-opening goal in the third minute of a friendly match against South Korea on June 15, 2013, near her hometown in Massachusetts.

Following a five-year absence, she was called back up to a USWNT talent identification training camp in December 2019 by new coach Vlatko Andonovski.

[45] In October 2020, after winning the Challenge Cup with the Houston Dash, Mewis credited her improvement in form to the process of recovering from an anterior cruciate ligament injury she suffered in 2018, particularly citing how it forced her to re-evaluate her competitive mentality.

[46] On June 21, 2023, Andonovski named Mewis to the United States squad for the 2023 FIFA Women's World Cup in Australia.

[47] While she did not feature during the group stage, she made her first World Cup appearance during the game against Sweden, coming on in the last minute of extra time before the penalty shootout.

[52] Mewis appeared in the Netflix documentary series Under Pressure, which follows the U.S. women's national soccer team as they compete in the 2023 World Cup.