Prior to taking up photography Mather, an orphan, earned her living as a prostitute. An accomplished photographer by the time she met Edward Weston, in 1912, Margrethe influenced him greatly, and they became partners in a studio in the Hollywood-Pasadena area. Her photographs appeared in various photography periodicals, and her image appeared frequently in Weston's photographs. From 1934 until her death Mather dealt in antiques and occasionally photographed friends.
Working with an 8 x 10 view camera, Mather almost always contact-printed her silver and platinum photographs. She made portraits of friends and celebrities, such as Sadakichi Hartmann, Johan Hagemeyer and, of course, Weston.
Margrethe was influenced by the anarchist philosopher Emma Goldman, whose lectures she attended.