Mendoza, who was cast at the villain Arachne, suffered a head concussion in December after a piece of equipment hit her in the head backstage.
Actress T.V. Caprio has been hired to replace Mendoza, who left the show last week, according to. The Hollywood Reporter.
Caprio is perhaps best known for appearing in musical director Julie Taymor's film Across the Universe. The Spider-Man role will mark Caprio's Broadway debut.
The musical saw several delays before and during production, and has been troubled by set injuries and disastrous preview performances.
Stuntman Christopher Tierney was hospitalised recently after falling from scenery during a preview showing. He is currently recovering from back surgery.