Sakina Bibi, 38, and her daughter, Rizwana, 16, had been giving drops to children when two gunmen on a motorcycle opened fire, police said.
No group has said it was behind the attack.
However, Islamist militants oppose vaccination, saying it is a Western conspiracy to sterilise Muslims.
Police said that the vaccination team had not been given security as in the past the police presence had drawn attention to their work.
Police official Naseebullah Khan said the women had been part of a major immunisation campaign in Balochistan province, of which Quetta is the capital.
“They died on their way to a hospital,” he said.
Balochistan chief minister Mir Abdul Qudus Bizenjo condemned the shooting as an act of “cowardice and terrorism”.
“An attack on those working to serve the people is an attack on humanity,” he added.
Scores of people have been killed in recent years in militant attacks on polio immunisation campaigns.
In January 2015 a suicide bombing in Quetta killed 15 people outside a vaccination centre in Quetta. The Pakistani Taliban and another militant group, Jundullah, claimed to have been behind that attack.
Pakistan is one of only three countries in the world, along with Nigeria and Afghanistan, that have failed to prevent the transmission of polio, according to the World Health Organization.
Pakistani Prime Minister Shahid Khaqan Abbasi ordered authorities in Balochistan to step up security around the polio teams. (Courtesy BBC)