In 1991, The New York Times revealed that George H. W. Bush was suffering from Graves' disease, a non-contagious thyroid condition that his wife Barbara also suffered from.

On February 24, 2000, Bush was standing at a reception for 90 minutes when he felt lightheaded. He was admitted to a hospital with an irregular heartbeat. When Bush was released three days later, his doctors said that he had retained the irregularity in his heartbeat. On March 11, 2007, Bush fainted on a golf course and was admitted to the Eisenhower Medical Center in Rancho Mirage, California, but was released the following morning.

In July 2015, Bush suffered a severe neck injury. At age 91 in October that year, he was wearing a neck brace in his first public engagement since the accident when he threw the ceremonial first pitch for the Houston Astros at Minute Maid Park. Bush wrote a letter to president-elect Donald Trump in January 2017 to inform him that because of his poor health, he would not be able to attend Trump's inauguration on January 20; he gave him his best wishes. On January 18, he was admitted to the intensive care unit at Houston Methodist Hospital, where he was sedated for a procedure to treat an acute respiratory problem that was stemming from pneumonia. Three months later, he experienced a recurrence of pneumonia and was hospitalized.

On November 25, 2017, Bush became the longest-lived U.S. president when he surpassed the 93 years and 165 days lifespan of Gerald Ford, who died in December 2006. Upon Ford's death Bush had become both the nation's oldest living president as well as the oldest living vice president; on June 12, 2018 he became the first U.S. president to reach the age of 94.

On April 22, 2018, the day after his wife's funeral Bush was hospitalized with a blood infection. The infection led to sepsis. One month later, he was briefly hospitalized again, after experiencing fatigue and low blood pressure.

Bush suffered from vascular parkinsonism, a form of Parkinson's disease which had forced him to use a motorized scooter or wheelchair since at least 2012.