Hope died Monday at her Toluca Lake home of natural causes, publicist Harlan Boll said.
In the late 1960s, the Hopes donated 80 acres of land near their future Palm Springs estate for the medical center, which opened in 1971.
PHOTOS: Dolores Hope | 1909 - 2011
They became "the driving forces behind the creation and long-term growth" of the medical facility, the center said on its website.
She served as chairwoman of the center's board for years, and he raised millions for the center through the annual professional golf tournament that for years bore his name.
"It was Mrs. Hope's vision that started this institution and she has worked for over 25 years to make it a reality," Albert C. Mour, then president of the medical center, wrote in The Times in 1990.
When her husband died in 2003 — two months after turning 100 — Dolores declined to estimate how many millions they had given or raised for charity. She did say most of it involved young people.
A great deal of their fortune came from vast property holdings in the San Fernando Valley. At Bob Hope's death, their wealth had been estimated at as much as $500 million. Their multimillion-dollar Palm Springs estate was built in 1979.
On her 100th birthday in 2009, she attended a party in the backyard of the Toluca Lake home that she and her husband bought in 1938. At the event, daughter Linda Hope theorized that laughter in the family home contributed to her parents' long lives.
She was born Dolores DeFina on May 27, 1909, in New York City and grew up in the Bronx.
During the 1930s, she sang in nightclubs using the stage name of Dolores Reade and met Bob Hope when he caught a New York City show.
After a brief courtship, they married in 1934 and were soon sharing the vaudeville stage.
While Dolores raised their four children, her husband's career took off and he was often away.
"When we were celebrating our 50th anniversary, people would say, 'Fifty years?' And Bob would say, 'Yeah, but I've only been home three weeks,'" Dolores said in 1995 in the Palm Springs Desert Sun.
To mark that half-century, she gave him a paperweight inscribed, "Don't think these three weeks haven't been fun."
Bob later said he enjoyed the stability of having a home to return to. He recalled how his children would listen to his jokes while Dolores, who was a devout Catholic, decided if they were appropriate for a family audience.
"I learned to temper my humor in those years," he said. "Dolores was a tough critic."
During the same interview, Dolores said, "We always had quality instead of quantity. ... When he wasn't home, he'd call almost every day, except when he was in a combat zone. Even then, he'd try."
In the late 1940s, Dolores began performing in her husband's famed overseas tours to entertain U.S. troops and later sang on many of his NBC television specials.
When Bob went to Saudi Arabia to entertain American troops in 1990, he was forced to leave many women out of the show. An exception was made for Dolores, who was allowed to sing "White Christmas" to the troops on Christmas Eve.
In addition to her daughter, Linda, she is survived by another daughter, Nora Somers; a son, Kelly; four grandchildren and a great-grandchild. Another son, Anthony, died in 2004.
Services will be private.
PHOTOS: Notable deaths of 2011