Clara and Ossip had a long distance friendship for many years including an on again, off again engagement.  Her mother died in 1905 and she had a "nervous breakdown."  In 1909, Clara and Ossip resumed their relationship when Ossip came to the Clemens home in Redding, Connecticut to recuperate from surgery he had in New York City.  By October that year they were married, just a short time before Samuel Clemens death in 1910.  As the only surviving Clemens child, she inherited all of her father's estate.  Clara was already pregnant with her only child, a girl, Nina, who Samuel never got to see.

The new family spent most of their time in Europe but in 1918 moved to Detroit, Michigan, where Ossip became the director of the Detroit's Symphony Orchestra, a position he held for the remainder of his life. Clara would occasionally sing and act in local theater groups but her professional performing days were over.

After a long career as director and a world renowned pianist, Ossip died in 1936 from stomach cancer, at the age of 58. He had a long painful illness and Clara and usually Nina were by his side.  However neither attended his funeral.  Soon after Clara and Nina sailed to Europe. In 1939 Clara moved to Los Angeles. Eight years after Ossip's death she remarried another Russian musician, Jacques Samossaud, whom she had met with Ossip years before he died.. She and Jacques moved to San Diego but they continued to visit Clara's Lucia relative, Ira Clemens Lucia,  in Detroit from time to time and to attend the Detroit Symphony. In 1962, at the age of 88, Clara died in San Diego.