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Whitford graduated from Reading Memorial High School in 1970. After attending the Berklee College of Music,rn Whitford played in local bands Cymbals of Resistance, Teapot Dome, rnEarth, Inc., and finally a band called Justin Thyme before joining rnAerosmith in 1971, replacing original guitarist Ray Tabano.rn Aerosmith would go on to be one of the most successful bands of the rn1970s. However, following a string of less successful albums in the latern 1970s, Whitford left the band in 1981 to work on his own project with rnsinger Derek St. Holmes, simply called Whitford/St. Holmes. The project was dissolved after a sole self-titled album was released in 1981.

Whitford briefly toured with The Joe Perry Project, featuring former Aerosmith band mate Joe Perry, before both Perry and Whitford rejoined Aerosmith in 1984. In the mid-late 1980s, all band members completed drug rehabilitation, including Whitford, who completed programs to combat his alcohol abuse. Whitford remains sober to this day and continues to be an active force in Aerosmith.

Whitford also served as a producer for a well-known Boston band, The Neighborhoods,rn who were led by a rabid Aerosmith fan, David Minehan. When, in 1994, rnWhitford was forced to leave unexpectedly in the middle of an Asian tourrn due to family illness, Minehan was flown to Japan where he performed inrn Whitford's place for several days until Whitford returned.

Whitford missed the start of Aerosmith's 2009 summer tour after rnrequiring surgery as a result of a head injury sustained while getting rnout of his Ferrari, joining the tour after a month.

In 2010, Whitford was announced as one of the guitarists to take part in the Experience Hendrix tour, playing songs performed and inspired by Jimi Hendrix along with other musicians such as Joe Satriani, Sacred Steel, Jonny Lang, Eric Johnson, Kenny Wayne Shepherd, Ernie Isley, Living Colour, Hubert Sumlin, Chris Layton, and bassist Billy Cox.

Along with fellow Aerosmith guitarist Joe Perry, Whitford was included in the Guitar World book The 100 Greatest Guitarists of All Time in 2007.

While Joe Perryrn is Aerosmith's more well-known guitarist and the band's principal rnsongwriter with Steven Tyler, Whitford has made significant rncontributions to the band's repertoire over the years. This includes rnco-writing Aerosmith's hit "Last Child" as well as some of Aerosmith's heaviest songs: "Nobody's Fault" and "Round and Round",rn and playing lead guitar on "Sick as a Dog" and "Back In the Saddle" (onrn which Perry plays six string bass), "Last Child", and on the ballads "You See Me Crying" and "Home Tonight".rn When Aerosmith made their comeback in the late 1980s, Whitford rncontinued to co-write tracks such as "Permanent Vacation" and "Voodoo rnMedicine Man", and plays occasional lead guitar on some more recent rntracks.

Said Aerosmith lead singer Steven Tylerrn of the two guitarists, "Joe is self-taught and his playing comes from rnraw emotion. Not that Brad's doesn't, but his style is more schooled."