The governor made the announcement Thursday morning during a press conference in Hardee County.
"I just wanted to let everybody know that the first lady yesterday, we completed the final chemotherapy treatment that she has to do," he said with a smile, as the crowd erupted with applause.
"It's not the most fun thing to see someone to go through, but at the end of the day, she's fought really hard, we think she's responded really well," DeSantis said. "Still got more stuff to do, but that's a big milestone, it's nasty stuff."
When he announced Casey's breast cancer diagnosis back in October, he said his wife wanted to be honest with people because of the prominent role she has played in her husband's administration, particularly on issues such as mental health and substance abuse services.
Casey DeSantis, 41, is the mother of three young children under the age of five.
"She got through that, she ran that gauntlet," the governor said. "She's doing well and we look forward to continue to have good news over the ensuing weeks and months."