During this incarnation, the Second Doctor confronted familiar foes such as the Daleks and the Cybermen, as well as new enemies such as the Great Intelligence and the Ice Warriors. It was during this time that he first met Alistair Gordon Lethbridge-Stewart, a military man who would later become the leader of the British contingent of UNIT, a military organisation tasked to investigate and defend the world from extraterrestrial threats.

The Second Doctor's time came to an end after he was put on trial by his own people, the Time Lords for breaking their laws of non-interference. Despite the Doctor's argument that the Time Lords should use their great powers to help others, he was sentenced to exile on 20th century Earth, the Time Lords forcing his regeneration into the Third Doctor in the process.

Based upon events in The Two Doctors, however, it is speculated by some that the Time Lords, recognizing the need for influencing other times and cultures, but unwilling to violate their stance against intervention, put off the sentence as long as the Doctor acted as an intergalactic troubleshooter for them. He did this for a time, but eventually he chafed at their control and tried to escape. He was promptly caught and his sentence of regeneration and exile enforced...