In November 2015, Melis signed a one-year contract with Seattle Reign FC in the National Women's Soccer League for the 2016 season, and was assigned the number 14 jersey. In an interview she said it was a dream come true to play in the US. Of her signing, Seattle's head coach Laura Harvey said, "Manon is a fantastic talent who will bring something new to our attack next season. We're thrilled to have a player with her experience and consistent record of success at the highest levels of club and international football join our club next season." Other stars playing for Seattle included 2011 FIFA World Cup winners Nahomi Kawasumi and Rumi Utsugi, 2015 World Cup winners Megan Rapinoe and Hope Solo, as well as Kim Little. Melis was amazed at the popularity of women's football in the US, exemplified by how her teammate Solo had to travel with a hoodie and sunglasses to avoid attention. Seattle's season got off to a bad start with a home defeat to Melis's old club Sky Blue, ending their streak of 24 undefeated home games, in front of a crowd of 4,000. In the next game, away at Boston Breakers, she scored her first goal in the US, in a 3–0 win. In May, in a game against Portland Thorns FC, she fractured her tibia after landing wrongly on the pitch. She joined Rapinoe and Jess Fishlock on Seattle's injury list and missed the following four games. She came back strong from injury, scoring five goals in five matches. On 25 September 2016, she played the last game of her career, in front of over 5,500 people. She scored in the 60th minute to help Seattle to a 3–2 away win over Houston Dash. Seattle finished the season in fifth place, narrowly missing out on a spot in the play-offs. In 16 appearances she scored seven times and was the club's leading scorer that season. Houston's Kealia Watt topped the league's scorer's list with 11 goals. In November 2016, Melis announced she had decided to retire from professional football.