He was reportedly defending his family after three men broke into the family home in Coorparoo around 3am (AEST) on Monday morning.
According to Channel 7, neighbours were woken and raced to the scene to help, holding down one of the alleged offenders who was arrested at the scene.
According to a Queensland Police statement, two men are in police custody. Further offenders fled in a car toward Woolloongabba.
Sunrise's Brisbane correspondent Bianca Stone reported Monday morning Kefu is "fighting for life".
She described the incident as a "stabbing rampage" and a "large brawl" when speaking on Channel 7 Monday morning.
The statement released by Queensland Police confirmed a "violent" altercation left four members of the home injured.
"Police have two males in custody following a burglary and wounding in Cooparoo this morning," the statement read.
"Police were called to Buena Vista Avenue at around 3am in relation to an incident.
"Early information suggested a number of males were disturbed breaking into a dwelling there and a violent altercation left four members of the house injured.
"One male was restrained and taken into custody at the scene.
"Further offenders fled in a car toward Woolloongabba.
"The four injured residents were transported to the Princess Alexander Hospital for treatment. A man in his 40s has serious injuries. Investigators urge witnesses to contact police."
Kefu's wife suffered a significant arm injury, while his son suffered lacerations to his back and abdominals. His daughter suffered a hand injury.
Kefu played 60 times for the Wallabies, including winning the World Cup in 1999, and made 103 appearances for the Queensland Reds during his career.
He became a cult hero when scoring one of the most iconic tries in Bledisloe Cup history in the 2001 series when his last-minute try saw the Wallabies win the Cup.
He is currently the head coach of the Tongan national team.
Rugby world, teammates offer prayers for Kefu
Former teammates and international rugby stars have taken to social media to show public support for the former No. 8 lock forward.
Code-hopping superstar Sonny Bill Williams wrote on Twitter: "Thoughts and prayers are with my Tongan brother Toutai Kefu & his family".
Wallabies great Tim Horan, Kefu's former teammate, posted on Twitter: "Thoughts and prayers to Kef and the family".
Another of Kefu's former Wallabies teammates Owen Finegan wrote: "This is crazy stuff. Thoughts and prayers with Kef and his family".
Former Wallaby and current member of the Tongan international team coached by Kefu, Cooper Vuna wrote: "Keep fighting coach! We are all here with you. Ofa Atu Toutai Kefu".
Former Wallaby Digby Ioane also posted a message with heart and prayer symbol emojis.
Former Wallaby Matt Cockbain posted: "Just awful, thinking of the Kefu's".
The official Wallabies Twitter account also offered its support: "You got this great man!! All our love and thoughts to you and the entire Kefu family".