It was Portman's first win in two nominations and follows her supporting actress nomination for "Closer," which was made in 2004.
Portman, 29, who lost 20 pounds in the year she prepared for the film, wore a deep purple off-the-shoulders dress on the red carpet, to accommodate her growing baby bump.
In December, Portman and her fiance Benjamin Millepied, the choreographer of "Black Swan," announced that she was pregnant. They met on the set of the film, a psychological thriller that verges into horror territory, directed by Darren Aronofsky.
Millepied helped her up the steps to the stage of the Kodak Theatre to accept her award. Portman called him "my beautiful love," who "has now given me my most important role."
Portman had been the heavy favorite to win, having swept the awards season in earlier match-ups such as the Screen Actors Guild Awards when she was up against Annette Bening in the same category.
Bening, 52, did not capitalize on her fourth Oscar nomination for her portrayal of a stern but over-drinking lesbian mother whose partner cheats on her in "The Kids Are All Right." She has been nominated three times for best actress and once for supporting.
Others nominated for the prize were Nicole Kidman, with her third nomination for playing a bereaved mother in "Rabbit Hole"; Michelle Williams, with her second for a woman whose marriage is on the rocks in "Blue Valentine"; and Jennifer Lawrence, with her first for playing a woman who fights a rural meth-cooking community to save her family in "Winter's Bone."
