Information about the type of gene action governing the inheritance of cowpea seed flavonoid content and antioxidant activity is prerequisite for starting an effective breeding program for developing improved varieties. For this purpose, half-diallel crosses among seven diverse parents were made. The homozygous parents and 21 F1 hybrids were evaluated at Maroua in the Sudano-Sahelian zone of Cameroon using a randomized complete block design with three replicates. Flour samples produced from decorticated seeds were used for biochemical analysis. Analysis of variance showed significant differences (P < 0.001) among genotypes for the studied traits with ranges of 363.6–453.9 mg rutin equivalent per 100 g dry weight (DW) for total flavonoids, 13.38–30.73 mg ascorbic acid equivalent per 1 g DW for ferric iron reducing activity, 70.98–266.93 mg trolox equivalent per 100 g DW for 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and 90.93–370.62 mg trolox equivalent per 100 g DW for 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging activity. Both additive and non-additive gene effects were significant in the genetic control of these traits, but dominance variance was greater than additive variance. The traits were mainly controlled by overdominance model suggesting a selection in the delayed generations. Broad- and narrow-sense heritability estimates varied from 0.90 to 0.99 and from 0.12 to 0.45, respectively. The variances due to both general and specific combining ability were highly significant for all studied traits. Recessive alleles had positive effects on DPPH and ABTS scavenging activities, whereas dominant alleles had positive effects on flavonoid content and ferric iron reducing activity. These results could help cowpea breeders to improve the antioxidant potential of cowpea seeds by appropriate selection.