During her journeys with Tegan and Adric aboard the TARDIS, Nyssa finds herself trapped in a mathematical equation by the Master – whom she hates as he is, of course, now using "that face" (her father's). She also encounters a race of androids and their insane ruler, helps foil the genocidal plans of a wounded Terileptil and incidentally start the Great Fire of London, and discovers her remarkable resemblance to Ann Talbot.
Adric's death while battling the Cybermen affects the TARDIS crew deeply. When confronted by an illusion of Adric created by the Master shortly afterwards, both Nyssa and Tegan are initially taken aback, until they see through the deception when Nyssa sees Adric is still wearing his now-destroyed badge. During this adventure, Nyssa also displays a previously unseen psychic ability when she is contacted by the Xeraphin.
Nyssa travels alone with the Doctor for an unspecified period of time when the Doctor leaves Tegan at Heathrow. Although no televised adventures take place in this period, several spin-offs including those by Big Finish Productions and BBC Books' Past Doctor Adventures are set in this gap.
Nyssa and the Doctor are reunited with Tegan while battling against Omega in Amsterdam and on Gallifrey, help Tegan battle her inner demons as personified by the Mara, and meet the Doctor's old friend and ally Brigadier Lethbridge-Stewart. It is during this adventure that she and the TARDIS crew meet Turlough, posing as a typical English schoolboy. When the TARDIS crew arrive on the derelict space station Terminus, Nyssa's adventures with the Doctor come to an end, as – to Tegan's horror – she elects to stay on board the Space Station in order to help free the enslaved guards and turn the station into a real hospital. The Doctor is moved by this noble gesture and parts saying that he thinks she is very brave. Nyssa's deep affection for the Doctor is demonstrated at this point when she kisses the Doctor goodbye.
Since then, Sutton has also voiced Nyssa in several audio plays alongside Peter Davison as the Fifth Doctor, produced by Big Finish Productions. The audio play Primeval, which is set in Traken's past, provides an explanation for Nyssa's sudden collapse at the end of Four to Doomsday and her apparent development of psychic abilities in Time-Flight. The canonicity of the audio dramas, like other Doctor Who spin-off media, is unclear.