Bird was a sickly child and spent her entire life struggling with various ailments. Much of her illness may have been psychogenic, for when she was doing exactly what she wanted she was almost never ill. Her real desire was to travel. In 1854, Bird's father gave her £100 and she went to visit relatives in America. She was allowed to stay until her money ran out. She detailed the journey anonymously in her first book The Englishwoman in America, published in 1856. The following year, she went to Canada and then toured Scotland, but time spent in Britain always seemed to make her ill and following her mother's death in 1868 she embarked on a series of excursions to avoid settling permanently with her sister Henrietta (Henny) on the Isle of Mull. Bird could not endure her sister's domestic lifestyle, preferring instead to support further travels through writing. Many of her works are compiled from letters she wrote home to her sister in Scotland.
Bird's time in the Rockies was enlivened especially by her acquaintance with Jim Nugent, a textbook outlaw with one eye and an affinity for violence and poetry. "A man any woman might love but no sane woman would marry", Bird declared in a section excised from her letters prior to their publication. Nugent also seemed captivated by the independently-minded Bird, but she ultimately left the Rockies and her "dear desperado". Nugent was shot dead less than a year later.
At home, Bird again found herself pursued, this time by John Bishop, an Edinburgh doctor in his thirties. Predictably ill, she went travelling again, this time to the far east: Japan, China, Vietnam, Singapore and Malaysia. Yet when her sister died of typhoid in 1880, Isabella was heartbroken and finally accepted Bishop's marriage proposal. Her health took a severe turn for the worse but recovered by Bishop's own death in 1886. Feeling that her earlier travels had been hopelessly dilettante, Bird studied medicine and resolved to travel as a missionary. Despite her nearly sixty years of age, she set off for India.
Featured in journals and magazines for decades, Bird was by now something of a household name. In 1892, she became the first woman inducted into the Royal Geographical Society. Her final great journey took place in 1897 where she travelled up the Yangtze and Han rivers which are in China and Korea, respectively. Later still, she went to Morocco, where she travelled among the Berbers and had to use a ladder to mount her black stallion, a gift from the Sultan. She died in Edinburgh within a few months of her return in 1904, just shy of her seventy-third birthday. She was still planning another trip to China.
"There never was anybody," wrote the Spectator, "who had adventures as well as Miss Bird." In 1982, Caryl Churchill used her as a character in her play Top Girls. Much of the dialogue written by Churchill comes from Bird's own writings.