Hanson was born in Tulsa, Oklahoma. He sings and plays guitar in the band Hanson. He and his younger brother, Taylor, started the band, initially known as The Hanson Brothers (later changed to just 'Hanson'), in 1992. Isaac was eleven, Taylor nine, and Zac six. They performed as an a cappella group outside clubs in their hometown of Tulsa. On May 6, 1997, the band released Middle of Nowhere, their first album with a major label and their third studio album overall . The first single, "MMMBop", made it to number one on the Billboard Hot 100 chart. May 6 has been declared "Hanson Day" in the brother's hometown of Tulsa, in honor of the release of Middle of Nowhere.

Isaac married Nicole Dufresne (born November 25, 1983) of Panama City, Florida, on September 30, 2006 in Tulsa in a ceremony in front of 300 guests. Isaac met Nikki after spotting her in the 5th row of a crowd at their 2003 New Orleans concert.

Isaac and Nikki's first child, Clarke Everett Hanson, was born on April 3, 2007 weighing 8lb 12oz. The couple welcomed their second son, James Monroe Hanson on July 1, 2008. He weighed 8 lbs. 11oz at birth. Both of their sons go by their middle name, following in their father's steps.

On October 3, 2007, Isaac was hospitalized with a pulmonary embolism after suffering severe shoulder and chest pains. He was rushed into emergency surgery, according to Tulsa World, and subsequently underwent a speedy recovery. Isaac was diagnosed with venous thoracic outlet syndrome, a potentially fatal condition commonly referred to as Paget-Schroetter Syndrome. In December 2007, Isaac underwent surgery at Baylor University Medical Center in Dallas, Texas to remove a rib that was obstructing blood flow to the arm.

3 Car Garage · MMMBop: The Collection · 20th Century Masters - The Millennium Collection: The Best of Hanson · Middle of Nowhere Acoustic' ·