Johnston was born in Collingwood, Ontario Canada, and grew up in British Columbia. Her father was a jeweller, her mother a calligrapher and bookkeeper.
Johnston attended the Vancouver School of Art — hoping to make a career as an artist. Her main interest was animation. After two years of Art College, she took a job in an animation studio in Vancouver, where she worked in the ink and paint department, and began to apprentice as an animator.
Shortly after getting married, she moved to Ontario in 1969, and got a job as a medical illustrator at McMaster University.
In 1972 she discovered that she was expecting her first child, Aaron, and left McMaster to work at home. Her obstetrician challenged her to do some drawings for the ceilings above his examining tables. These were published in a book called "David, We're Pregnant," which sold over 300,000 copies.
Shortly after the publication of her first book, she was divorced and worked as a commercial artist — free-lancing from a greenhouse she had turned into a studio.
In 1975, "Hi Mom, Hi Dad" was published, a sequel to "David." By this time she was remarried. She continued to freelance until her daughter Katie was born. "Do They Ever Grow Up?" was the third publication in her first sequence of books about parenting. Not long after this book was published, the Johnston family relocated to Lynn Lake, Manitoba.
In 1978, Universal Press Syndicate saw the three books, and asked if Johnston was interested in doing a daily comic strip. She signed a twenty-year contract, and the work on For Better or For Worse began.
Today, Johnston lives in Corbeil, Ontario. She was the first woman to receive a Reuben Award for Cartoonist of the Year by the National Cartoonists Society in 1985. She has been nominated for a Pulitzer Prize, has received the Order of Canada, and claims a star on Canada's Walk of Fame.
For Better or For Worse has been syndicated since 1979, and was named Best Syndicated Comic Strip in 1992. For Better or For Worse appears in more than two thousand newspapers in twenty-three countries, and is translated into eight languages for a devoted readership of more than 220 million. The strip continues to appear in newspapers as reruns, and also boasts a lively web presence at www.fborfw.com