The Voice coach, 39, and former Nashville Star finalist, 31, wed in May 2011 after six years of dating.
"This is not the future we envisioned," the couple said in a statement released to media outlets on Monday.
"And it is with heavy hearts that we move forward separately. We are real people, with real lives, with real families, friends and colleagues. Therefore, we kindly ask for privacy and compassion concerning this very personal matter."
The couple met in 2005 at a CMT event while Shelton was still married to his first wife, Kaynette Gern, according to Us Weekly. Shelton divorced Gern in 2006, and he and Lambert reportedly began dating shortly thereafter.
Rumors of infidelity and marital trouble had swirled around the couple for years, however Shelton and Lambert had repeatedly denied them.
"[I tell Miranda], 'I have nothing to hide from you,'" Shelton told People in 2013.
"That's always been our policy: 'Here's my phone. Go through it.' -- That's really the kind of trust we have -- There are no secrets. [I'll say], 'Go dig through my drawers or my computer if you feel like you need to.' And that's been a really good thing, because I don't want her to ever have any doubts."