While speaking at an event at the Odeon cinema in Leicester Square, the 65-year-old Prince was interrupted by a baby crying in the audience.
"I think that baby needs something, a bottle perhaps," jovial Charles told the crowd. "I know these things, I'm taking lessons in grandparenting."
Prince Charles arriving in Leicester Square
The Prince of Wales' comment came during his speech at the Prince's Trust & Samsung Celebrate Success Awards, where he was joined by stars including X Factor winner Sam Bailey, Joan Collins, Tess Daly, Vernon Kay, Pixie Lott and The Hobbit star Luke Evans.
Jools Holland, Philip Schofield, Ant and Dec and the members of dance group Diversity also attended the ceremony.
The heir-to-the-throne, who teamed a light grey suit with a pink silk tie and pocket handkerchief, appeared to be in high spirits as he awarded 21-year-old Carly Williams from Weston-Super-Mare with the Samsung Young Achiever of the Year Award.
The Prince of Wales presents Carly Williams with her award
Charles, who became a grandfather for the first time when George was born on 22 July 2013, may have been tasked with helping to look after the royal tot while William and Kate are on holiday.
Prince Charles joins British royals and stars paying tribute at Sir David Frost's memorial service
The Duke and Duchess of Cambridge jetted off to The Maldives last Thursday, leaving their seven-month-old son in the care of his new nanny and grandparents Carole and Michael Middleton.
Proud mother Kate with Prince George at his christening
Young George was spotted out in Hyde Park with his new Spanish nanny, who is said to be being shown the ropes by Kate's mother Carole.
Exclusive details on Prince George's new nanny
With George not far from Prince Charles' official London residence, Clarence House, the proud grandfather may have paid the youngster a visit or two while William and Kate are away.