In the bout that will air in the U.S. July 1 at 7 p.m. PDT, Pacquiao (59-6-2, 38 knockouts) will be fighting live on network television for the first time since 2005.
The seven-division world champion will defend his World Boxing Organization welterweight belt at Brisbane's Suncorp Stadium with a crowd of 55,000 expected to see if Horn (16-0-1, 11 KOs) can produce a stunning upset.
The bout could move Pacquiao, who serves as a senator in the Philippines, closer to a later 2017 date against unbeaten two-belt junior-welterweight champion Terence Crawford.
ESPN President John Skipper, in a prepared statement, said the bout is "a significant moment for ESPN and for boxing fans."
The card includes a co-main event featuring 2016 Irish Olympian Michael Conlan, and as Top Rank Chairman Bob Arum has rounded up more young talent, like U.S. Olympian Shakur Stevenson, the ESPN relationship is expected to provide a more expansive showcase for talented fighters.
While HBO has withdrawn from non-pay-per-view cards this year, Arum now has an alternative promising a wider audience for fighters such as his super-featherweight champion Vasyl Lomachenko and featherweight champion Oscar Valdez.
The ESPN broadcast team will feature
And ESPN Deportes' coverage will include analysis by Juan Manuel Marquez, who has fought Pacquiao four times.