Johnson joined AC/DC in 1980, after the death of band's former lead singer Bon Scott. He is credited with pushing the band in a more heavy metal direction, beginning with his first album with AC/DC, Back in Black, now regarded as a rock landmark and one of the five top-selling albums of all time. It and his subsequent albums with the group have made him one of the most recognized and emulated voices in rock music.

Before AC/DC, Johnson had joined the Newcastle glam-rock band Geordie in 1972. After a number of hit singles, the band split up in 1978 but Johnson re-formed it in 1980. Just after a record contract had been signed, Johnson was asked to audition for AC/DC. He got the job by singing the Ike and Tina Turner song "Nutbush City Limits," and AC/DC's own "Whole Lotta Rosie", which was recorded in 1977 with Bon Scott. He was the band's first choice. Unbeknownst to Johnson, a fan in Cleveland, Ohio had sent a Geordie album to AC/DC shortly after Bon Scott's death, urging them to consider him. And years earlier, Bon Scott himself had also praised Johnson's singing and energetic performance style to the rest of AC/DC after seeing Geordie play. (According to legend, this was the night Johnson was rushed to hospital after the show to have his appendix removed, which accounted for his writhing around on the stage.)

For ten years, Johnson cowrote all of AC/DC's songs with the Young brothers until personal matters diverted him in 1990, when the band's album The Razor's Edge was being written. Johnson now handles all the lead vocals, for the band, with backing vocals by Malcolm Young, Cliff Williams, and occasionally Angus Young when performing "T.N.T.".

Johnson's sartorial trademark is that he is seldom seen in public without a cap, pulled down above his eyes. Originally, he wore a flat cap, once regarded as a symbol of Tyneside (Bryan Ferry wears one on the back of his album Taxi), but in recent years, he has generally worn a baseball cap instead. Despite the headgear, he has a full head of hair.

Johnson's father was a Sergeant Major of the British Army's Durham Light Infantry; his mother came from Italy. Johnson credits his father for giving him his shouting voice.

Johnson's marriage, which produced two children, ended in divorce shortly before he joined AC/DC.

He made a cameo in the film Goal!, directed by Danny Cannon, as a Geordie watching a Newcastle United match at a bar in Los Angeles (his name is misspelled "Bryan" in the credits).