Prior to their first encounter, Margaret was already a fervent admirer of her husband-to-be, Sir William Huggins. William was an astronomical spectroscopist, whose line of work collaborated instantly with Margaret's. Their partnership was described as being "one of the most successful husband and wife partnerships in the whole of astronomy".
After their marriage on 8 September 1875, at the Monkstown Parish Church, the "two star-gazed" lovers devoted themselves to their research and their inspiring companionship resulted in an array of astronomical findings. Margaret and William Huggins were the first to "observe and to identify the series of hydrogen lines in the spectrum of the star Vega." The pair's detailed notebook entries contributed to their first paper publication in 1889, discussing the "studies of the spectra of planets". They were also among those who "observed the Nova of 1892, Nova Aurigae." Margaret was specifically in charge of the visual observations, while together they collected "photographic spectra over several nights."
The couple's work had a major influence on their daily lives. Their home acted more as a work space, rather than a place for any kind of familial essence, and they never had any children. In 1903, Margaret and William Huggins published their final piece of joint scientific research on the spectra of certain radioactive substances.