Born in Salem, Oregon, Cassandra Webb is a paraplegic and is blind after being struck with myasthenia gravis, a disease that erodes the nervous system. She was connected to a life support system made by her husband. She knows Spider-Man's secret identity and helps him occasionally. She is the grandmother of the fourth Spider-Woman, Charlotte Witter.
Major Story Arcs
Madame Web contacted the superhero known as Spider-Man and became somewhat of a mentor to Peter Parker (Spider-Man). She sent him on courses that would send him through many mental and physical challenges, but always managed to get out of it a better man. She is also found several times telling him that there is coming a time were he will be the only hope for human kind.
When that time comes Madame Web introduces Spider-Man to a galactic entity known as Mr. Universe. He with the help of Madame Web has been studying human society on Earth along with many other worlds and has found a confusing phenomena known as good and evil. Madame Web tries to explain to Mr. Universe the good is the only thing that keeps the world in balance but Mr. Universe will not be persuaded. He chooses a world that is totally at peace and has no knowledge of evil, and sends the villains Dr. Octopus, Dr. Doom, and Red Skull there, and allows one year's time to pass. During this time, the planet is devastated and taken over by the villains. It is then Spider-Man's job to lead a group of super heroes to defeat them, proving which is more powerful, and therefore better, good or evil.
Gauntlet and Grim Hunt
During the Gauntlet story arc of Amazing Spider-Man, Madame Web is kidnapped by Ana Kravinoff and tortured by her mother Sasha Kravinoff. She is present during the sacrifice of Mattie Franklin who was killed to resurrect Sasha's son Grim Hunter. After the resurrection of Kraven, Madame Web taunts Sasha saying that her plan is failing and that Spider-Man will defeat her and her family. Enraged at this, Sasha cut Madame Web's throat with a knife and leaves her for dead. When Spider-Man arrives she transfers her powers to Julia Carpenter just before dying. Julia then becomes the new Madame Web.
Madame Web has the psychic abilities: telepathy, clairvoyance, and prescience (the knowledge of all possible outcomes in a situation). She can perform psychic surgery and appear to others in astral form. After the ritual Gathering of the Five, she apparently has the gift of immortality, was de-aged, and cured of her myasthenia gravis.
Madame Web has passed away, but her influence has inspire others to make a temple of prophetic acolytes in her honor.
Ultimate Universe (Earth-1610)
In this universe, she is similar to her Earth-616 counterpart, only she appears younger. She is part of the psych team that plans to change Spider-Woman's memory. (Spider-Man's clone in this universe)
House of M (Earth-58163)
Madame Web is a therapist employed by SHIELD
Spider-Man The Animated Series
In the 1994 cartoon Spider-Man The Animated Series, Madame Web was a cosmic being whose power dwarfed that of Doctor Strange, and mentioned being from the same place as the Beyonder, who appeared with her. As per normal comic canon, she acted as an adviser to Spider-Man and helped him with cryptic clues and warnings.