The vote signals the latest in shifting attitudes that have swept across the staunchly Catholic country since the 2011 referendum to legalize divorce.
Since then, the country has introduced civil unions and last year became the first European state to ban “gay cure” therapy.
Last month, Prime Minister Joseph Muscat said gay marriage would be one of his priorities after he won a snap election.
“Malta wants to keep leading on LGBT issues and civil liberties, to serve as a model for the rest of the world,” Muscat told the BBC.
The changes are part of what the Maltese government hopes will be a modernization of marriage that will also allow gay couples to adopt children.
In the bill, references to “wife,” “husband,” “mother” and “father” all scrapped in preference of gender-neutral terms such as “parent” and “spouse.”
“The new law is the missing piece in the puzzle when it comes to family rights in Malta,” she said.
“The use of gender-neutral terms means that everyone is equal and it is much more inclusive, particularly when it comes to the trans community.”
While the measure is expected to pass, some lawmakers have said they would vote against it.
Since then, more than 20 other nations have followed suit, including Spain, Canada, Argentina, France, the United Kingdom, Germany, Ireland and the United States.
This story has been corrected to reflect that the vote is happening on Wednesday.