The 27-year-old – a key figure in the United States' 2019 World Cup triumph – joins the Club from National Women’s Soccer League outfit North Carolina Courage.
A skilful, creative and athletic attacking midfielder, who also possesses excellent aerial ability, Mewis boasts 67 caps and 18 goals for her country, including two strikes in France last summer.
She makes the move to Manchester in her first foray into the English game and will sport the number 22 shirt.
Speaking about her move, she said: “I'm so happy to have everything sorted. The opportunity came along at a really great time - as soon as I heard about the chance of coming to play for Manchester City, I was immediately interested.
“The Club is one of the best in the world and I've heard such good things about the women's side as a whole and the incredible facilities. I've followed the men's team too for a long time.
“This is a really cool, unique and amazing opportunity in my career and I'm so excited to come and see Manchester as a city, be a part of this incredible Club and hopefully help the team achieve their goals.”
Originating from a footballing family in Massachusetts - with her sister Kristie also playing professionally at Houston Dash - Mewis started out with UCLA Bruins where she won the National Championship as well as National Player of the Year honours.
In 2016, she won the NWSL Championship with Western New York Flash and at the start of 2017, linked up with North Carolina Courage and secured a further two league titles and three NWSL Shields in three years.
She was also named in the NWSL’s Best XI in her first year at Sahlen’s Stadium.
On the international scene, Mewis figured for the United States at numerous youth levels, winning the CONCACAF Under-20 Women’s Championship and FIFA U20 Women’s World Cup in 2012, before moving into the senior set-up in 2014.
Quickly becoming a key figure for the USWNT, the midfielder has helped the team to success in the SheBelieves Cup (2016 and 2020), Tournament of Nations (2018), CONCACAF Women’s Championship (2018) and most recently, the 2019 Women’s World Cup.
Head Coach Gareth Taylor said: “We’re thrilled to welcome Sam to Manchester City and we’re thoroughly looking forward to working with her.
“As well as being a World Cup winner, she will bring a wealth of experience and quality to our squad and I’m really pleased that she feels she can fulfil her ambitions with us.
“She will also be a fantastic addition to the Barclays FA Women’s Super League as a whole and we can’t wait to see her pull on a blue shirt for the first time.”
Head of Women’s Football, Gavin Makel, added: “Bringing Sam to the Club is a huge coup for us.
“She is a proven winner, having experienced incredible success with the USWNT last summer and of course at North Carolina Courage over the last few years in the NWSL.
“Having seen Sam play up close whilst in the US, she is a highly technical and extremely athletic midfield player who will help the team push on in what is a new era for the Club.”