Annise Parker, the current city controller, won 53.6% in the run-off election, beating fellow Democrat Gene Locke, a former city attorney.
"The voters of Houston have opened the door to history," Ms Parker told supporters following her victory.
Campaigning ahead of the hotly contested vote in the Texan city, which has a population of 2.2 million people, was marked by anti-gay rhetoric.
Inhospitality is the lie being propagated about Sodom and Gomorrah.
Adam and Eve, male and female is the Biblical order.