At least 12 people have died as a result of the overdoses administered to patients at the Jean Monnet hospital in Epinal in northeastern France between 2001 and 2006.
Dozens more are seriously ill as a result of calibration errors that produced the most serious radiation overdose incident France has known.
The doctors and the radiophysicist were convicted of manslaughter, failure to help people in danger and destroying evidence.
As well as being jailed for 18 months the 54-year-old radiophysicist Joshua Anah was fined €10,000 and banned from practising in the medical profession for five years.
The two doctors Jean-François Sztermer, 64 and Michel Aubertel, 62, were handed €20,000 fines on top of their prison terms. They were also slapped with lifetime bans on practising medicine.
Four others were acquitted by the court who had been charged in connection to the case.
The overdoses, which were given to patients diagnosed with prostate cancer, is believed to have been caused by two different malfunctions in the radiotherapy department at the hospital.
Firstly wrong measurements were initially programmed into new software and secondly the overdoses were not picked up in the final calculations of the doses before treatment was given.
The first malfunction caused doses of radiation to be administered to 24 patients at 20 times the level they should have been and 424 victims were given doses between 8 to 10 percent higher than intended.
The prosecutor had not argued for the two doctors to be convicted of manslaughter but the court still upheld that charge.
In his closing remarks, the chief prosecutor delivered a damning indictment of the doctors' "desire to hide the truth from the victims and their attempts to play down, even disguise their mistakes."
Throughout the case, lawyers representing the victims accused the doctors of playing God with their patients' lives and trying to bolster their professional reputations by using experimental techniques without taking the sufficient precautions.
The doctors blamed the mistakes on staff shortages and bureaucratic complexity of the rules surrounding radiation therapy.
Gerard Welzer, a lawyer who represented many of the victims, said he was very happy with the outcome.
"When it comes to the public health system these days, convictions are becoming more and more rare," he said outside court.