There is little information on the mating systems of Zygodontomys brevicauda. However, members of the subfamily Sigmodontinae generally have promiscuous mating systems. However, Akodon azarae is polygynous females mates with a single male and males attempt to mate with as many females as possible.

Zygodontomys brevicauda is unique in that it breeds throughout the year non-seasonally. Short-tailed cane mice do not respond to changes in photoperiod; instead, mating habits are related to resource availability or social cues. Ovulation is spontaneous, and gestation typically lasts for 25 days. Litter size ranges from 1 to 11 pups, but generally consists of about 5 pups. Females exhibit post-partum estrus and experience no delay in implantation due to lactation.

Neonates are born altricial, without hair and teeth, but digits are separated. Young develop juvenile pelage around the 5th day after birth and open their eyes on the 6th or 7th day following birth. Females become mature by 25.6 days after birth, and males become mature by 42.3 days. The presence of adult males increases the rate of uterine growth in young females.

Breeding season: Short-tailed cane mice breed non-seasonally throughout the year.

Range number of offspring: 1 to 11.

Average number of offspring: 4.6.

Average gestation period: 25 days.

Range birth mass: 3 to 4 g.

Range weaning age: 9 to 11 days.

Average age at sexual or reproductive maturity (female): 25.6 days.

Average age at sexual or reproductive maturity (male): 42.3 days.

Key Reproductive Features: iteroparous ; year-round breeding ; gonochoric/gonochoristic/dioecious (sexes separate); viviparous ; post-partum estrous

Zygodontomys brevicauda constructs nests from grasses and fallen plant material under tree roots, in holes, or on the bare ground. Females increase food intake during pregnancy to support the development of young and lactation. Young born are altricial and depend on their mother for food and protection in the days following birth. After birth, females nurse young for up to 11 days. Little is know of paternal care in Z. brevicauda; however, in the closely related genus Akodon, females become aggressive towards males shortly before birth and raise the litter on their own.

Parental Investment: altricial ; female parental care ; pre-fertilization (Provisioning, Protecting: Female); pre-hatching/birth (Provisioning: Female, Protecting: Female); pre-weaning/fledging (Provisioning: Female, Protecting: Female)