Thomas, from Arizona, made global headlines after he gave birth to three children after beginning to change from female to male.
He was in the process of becoming a man before he married Nancy Beatie in Hawaii in 2003 but retained female reproductive organs.
He became pregnant three times with donated sperm when Nancy was unable to have children.
The couple eventually moved to Arizona but their relationship soured and they sought a divorce a few years later.
However, their request to legally separate has only just been granted because of a complex wrangle which finally ended on Wednesday when a three-judge panel of the Arizona Court of Appeals ruled that their marriage was considered valid in Arizona because it wasn't a same-sex union.
Last year, a lower court judge denied the divorce request and ruled that Arizona's ban on same-sex marriages prevented the marriage from being recognised as valid.
Thomas, 40, was born a woman in Hawaii and as an adult had a double-mastectomy and chest reconstruction surgeries, and began testosterone hormone therapy and psychological treatment to become a man.
Sixteen months ago, Maricopa County Family Court Judge Douglas Gerlach concluded the marriage appeared to be a same-sex union because it was between a woman and a person who was capable of giving birth.
The family court judge also found he had no jurisdiction to handle the divorce request because there was insufficient evidence that Thomas was a man when he got married, even though he had his Hawaii driver's license and birth certificate changed to say he was a man.
The Arizona appeals court ruled that Thomas's marriage in Hawaii was valid and noted that he didn't withhold his transgender status from officials in Hawaii.
The panel said it was obliged to let people who get their birth certificates changed to reflect a new gender status the rights connected to their amended status - and doing otherwise would run afoul of equal-protection rights protections.
Shannon Minter, legal director for the National Center for Lesbian Rights, welcomed the decision, saying: "It's a precedent-setting case that will protect a lot of families."
Both sides in the Beatie case were pressing the courts to allow a divorce and made similar arguments.
Attorney David Michael Cantor, who represents Thomas, said the ruling will help his client close this chapter of his life, and it brings legal recognition to his marriage.
He said: "The state of Arizona has officially recognized him as a man and that his marriage was valid, and because his marriage was valid, his kids were born in wedlock, which is important to him."