Murillo spent two seasons with the San Siro club, but was deemed surplus to requirements by new Inter coach Luciano Spalletti.
"Valencia have reached an agreement with Inter for the transfer for two seasons with a mandatory purchase option for the Colombian international defender Jeison Murillo," a statement from the Liga side said.
Murillo became Valencia's second major signing on Friday, with the club having already snapped up Brazilian defender Gabriel Paulista from Arsenal, and both players will be presented on Saturday.
Valencia are also expected to complete a move for Murillo's former Inter team-mate Geoffrey Kondogbia, who has fallen out of favour at San Siro.
Head coach Marcelino has already snapped up goalkeeper Neto, forward Simone Zaza and winger Fabian Orellana in a busy transfer window at Mestalla.