The instruments, shown at a preview on Friday, include a 2005 Fender Stratocaster Signature Model, which is expected to sell for $20,000 to $30,000
Clapton used the instrument during the Cream Reunion concerts at the Royal Albert Hall in London in May 2005 and at Madison Square Garden in New York in October of the same year.
Another guitar, also expected to fetch as much as $30,000 at the sale at Bonham's on Wednesday, is a 2006 recreation of Clapton's famed Strat "Blackie", complete with cigarette burns on the headstock. In 2004, the original "Blackie" sold for $959,000.
Proceeds of the auction will benefit the Crossroads Centre in Antigua, which Clapton, a recovered alcoholic and former heroin addict, founded in 1998.
Clapton's collection of about 70 amplifiers are also for sale. One set of twin Fender amplifiers that he used in the 1980's, are expected to sell for as much as $12,000.
Another amp, a miniature Pignose from 1974, was possibly the same one used to record his song "Motherless Children".
Other items to be sold include a Versace suit worn by Clapton and a gold-records plaque given to Clapton for his album "Journeyman", which was released in 1989.
Two previous auctions have been held to benefit the Crossroads Centre, in 1999 and 2004.
Clapton, 65, is widely regarded as one of the best guitarists of all time. In 2004, Rolling Stone Magazine named him fourth on their list of the 100 best guitarists in music history.