Macario, who has 17 caps for the USWNT, arrives at the Women's Super League side on a three-year deal.
"Cat is one of the most intelligent, creative attacking players in the world," Chelsea boss Emma Hayes said in a statement.
"She brings a great deal of flair, European experience, and an unbelievable winning mentality. I think our fans will really love her."
Macario will not play any part in the 2023 Women's World Cup this summer with a ruptured anterior cruciate ligament that has kept her out for over a year.
The forward enjoyed an outstanding collegiate career at Stamford before turning professional and moving to women's football powerhouses Lyon in 2021.
Macario since helped the club to win both the French title and Women's Champions League.
'I can't wait to get started here," Macario said. "I'm really happy to sign for Chelsea and I hope to represent the jersey well over the next few years."