A 74-year-old woman was killed instantly when the vehicle failed to stop at a pedestrian crossing in Massa, on Italy's north-west coast.
An 81-year-old man died of his injuries in hospital, while at least two others were hurt, including the driver. One person is said to remain in serious condition.
The accident happened while it was still dark, at around 5 am. The group, made up of local pensioners, was setting off early for a coach trip to Prague.
The truck hit those at the front of the group in the centre of a zebra crossing, according to local newspaper Il Tirreno, which said that the impact was heard by people in nearby houses.
Witnesses said the scene looked like a "war zone".
The driver, a 43-year-old man from a neighbouring area of Tuscany, was arrested for vehicular homicide.
A drug test indicated that he may have taken cocaine, sources told La Repubblica, though police said they were waiting for final results to confirm whether he was under the influence of any substances.
His truck was transporting medicines at the time of the accident.