Tate tested positive for a performance-enhancing substance that he said came from prescribed fertility medication. His appeal was heard Tuesday by an arbiter in New York.
The suspension will cost Tate $465,000 in salary ($116,176 per game). He will miss the opener on the road against the Dallas Cowboys followed by games against the Buffalo Bills, Tampa Bay Buccaneers and Washington Redskins.
He will be allowed to participate in all preseason practices and games.
Tate's absence will put added pressure on a wide receiver corps that lost Odell Beckham Jr. in an offseason trade. Tate signed a four-year, $37.5 million deal as a free agent to help offset the loss.
Latimer is expected to slide into Tate's starting spot. He started in Thursday's preseason opener with Shepard still sidelined and caught two passes for 36 yards despite playing just two drives.
On Tuesday, before the decision was announced, Giants quarterback Eli Manning lauded Tate's ability and had hoped "things work out" for the receiver to play a full season.
"Golden is a smart player and he is going to be in the right spot and he has a good feel for the zones, how to get open versus different techniques and stuff," Manning said. "A veteran guy but also, we have seen a bunch of it with the Giants, his run after catch historically has been very good -- a playmaker. Hopefully, things work out and he will be here all year."
In a statement last month, Tate said he thought he had a legitimate case to win his appeal.
"This past April, during the off-season, my wife and I decided to see a specialist for fertility planning. I started the treatment prescribed to me and just days later I discovered it contained an ingredient that is on the league's banned substance list," Tate said. "I immediately discontinued use, I reported the situation to the Independent Administrator of the NFL Policy on Performance-Enhancing Substances, and I spoke with my coaches and general manager. I did all of this well before a failed test was even confirmed.
"Per NFL protocol, an initial suspension was imminent, but myself and the Giants organization are confident in the facts, and eagerly await my appeal to put this behind us."
However, the NFL's policy on performance-enhancing drugs is unforgiving. It states, "Players are responsible for what is in their bodies and a positive test will not be excused because a Player was unaware that he was taking a Prohibited Substance."
While with the Seattle Seahawks in 2013, Tate was critical of two teammates who received suspensions for substance abuse violations, calling them "selfish."
"You are affecting way more than yourself," Tate told 710 ESPN Radio at the time. "I feel like that was kind of a selfish move on both those guys' part. But it is what it is. The show must go on, and that's what we're gonna do."