Clapton announced news of the pregnancy Wednesday while at Buckingham Palace where he accepted a Commander of the British Empire award from Princess Anne, Britain's Mirror said.
"My wife is pregnant and she is expecting in January," Clapton said of his 28-year-old wife.
The couple has two other children, Julie Rose, 3, and 18-month-old Ella Mae.
Clapton also has a daughter, Ruth, 19, with previous girlfriend Yvonne Kelly.
The entertainer's son, Conor, died in 1991, when the 4-year-old fell from Clapton's New York apartment window.
Clapton wrote his hit song "Tears In Heaven" as a tribute to Conor.