President Michael D Higgins led messages of sympathy and condolences to the families of the dead and injured in the Berkeley tragedy.
The President was informed of the incident during an official visit to Italy and described the deaths as a "terrible loss of life" of young people.
"My heart goes out to the families and loved ones of all those involved," said Mr Higgins, adding that he had asked to be kept informed as further details emerge.
In the Dáil, Taoiseach Enda Kenny told a hushed chamber: "My heart breaks for the parents who have lost their children this morning."
The Taoiseach said his thoughts were also with other parents waiting fretfully for news from children who may be visiting California.
Mr Kenny said he had been contacted by the US Ambassador to Ireland, Kevin O'Malley, to relay the sympathies of the American people.
He said it was doubly tragic that such an incident could occur "at the start of a summer adventure" for young people.
Mr O'Malley said the American authorities were doing all they could to help the bereaved and the injured.
"All of us at the United States Embassy are greatly saddened by news of this tragic incident and are ready to do whatever we can to assist the Irish Department of Foreign Affairs at this difficult time," he said.
Foreign Affairs Minister Charlie Flanagan, who broke the news of the deaths, said: "This is a very challenging and difficult time for the families, for parents of those directly involved. It has been an appalling tragedy, an appalling loss of life.
"Young people with hopes and dreams for the future have suddenly been shattered."
He said the department's consular services, headed by Philip Grant, was assisting those affected and was at the scene of the tragedy.
Tánaiste Joan Burton said: "Hearing news like this about a loved one far away would be any parent's worst nightmare."
She added that everyone in Ireland was hoping the injured students would make a full recovery.
Student leaders said the deaths and injuries had left colleagues devastated.
"The thoughts and sympathies of the whole student movement in Ireland are with the families and friends of those young people caught up in this terrible event," USI president Laura Harmon said.
The Lord Mayor of Dublin Christy Burke will open a book of condolence for the victims at The Mansion House tomorrow and Friday from 10am to 4pm.
"It will be a chance for the people of Dublin to express their sympathies to the families involved," he said.