Andrade (26-0, 16 knockouts) dropped Kautondokwa four times in the first four rounds, once in the first and third, and twice in the fourth.
Glen Feldman and Marcus McDonnell scored the fight 120-104. Ramon Cerdan scored it 119-105.
In the first round, Andrade dropped Kautondokwa with straight left hand, while Kautondokwa was off balance.
Andrade sent Kautondokwa to the canvas again in the third with an overhand left that landed on the top of his opponent's head. The knockdown followed Kautondokwa's first significant offense of the fight, three punches to the body.
In the fourth, Andrade scored two more knockdowns, both with left hands to the head.
Andrade, of Providence, Rhode Island, previously held the WBO and World Boxing Association junior middleweight titles. He was also a member of the 2008 US Olympic Team.
Kautondokwa, the WBO African middleweight champion, dropped to 17-1 with 16 knockouts.
Kautondokwa, 32, was a replacement for Billy Joe Saunders. Saunders tested positive for oxilofrine, a stimulant, in a drug test administered by the Voluntary Anti-Doping Agency. The WBO stripped Saunders of his title after the Massachusetts State Athletic Commission declined to give him a license in a hearing on Oct. 9.
The fight was one of three world title bouts on the card.
In the co-main event, 2012 Olympic gold medalist Katie Taylor, of Ireland, retained her International Boxing Federation and WBA female lightweight titles with a 10-round unanimous decision over Cindy Serrano, of New York. All three judges scored the bout 100-90 for Taylor.
Tevin Farmer, of Philadelphia, defended his IBF super featherweight title, stopping James Tennyson of Belfast, Northern Ireland, in the fifth round.
In an IBF featherweight title eliminator, Kid Gallahad of Sheffield, England, won a 12-round unanimous decision over Toka Khan Clary of Providence, Rhode Island.
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