His superb innings of 132 proved the mainstay of Gloucestershire's total of 261 after Proteas skipper Francois du Plessis had won the toss and put the home side in on a drying pitch.
But a largely second string South Africa side were always in control of the chase and Wayne Parnell's hard-hitting 41 ushered the tourists to their target with six balls to spare.
In triumphal mood after winning the second Test at Lord's and displacing England at the top of the world rankings 48 hours earlier, South Africa sought to further stamp their authority ahead of the five-match one-day international series, which begins in Cardiff on Friday.
But the dress rehearsal did not go quite to plan as Housego, considered primarily a red-ball cricketer when he joined Gloucestershire from Middlesex last winter, set about reinventing himself in front of the County Ground's largest audience this year.
Far from helping the South Africans establish an important psychological advantage, this contest raised more questions than answers for the tourists as Housego offered England's batsmen much-needed encouragement.
Considered likely selections for the opening ODI at The Swalec Stadium, South Africa's spin triumvirate of Imran Tahir, Robin Pieterson and Faf du Plessis all suffered horribly at the hands of Housego and big-hitting James Fuller, who staged an explosive alliance of 94 in 12 overs for the seventh wicket as Gloucestershire recovered from 156 for six to post a competitive 261 in their 50 overs.
One of two members of South Africa's successful Test side on show at Nevil Road, Tahir's leg breaks went for 32 runs in five overs, while slow left armer Pieterson conceded 48 from nine and du Plessis 19 from two.